An indolylquinoline derivative promotes apoptosis in human lung cancer cells by impairing mitochondrial functions
We reported here that a synthetic indolylquinoline derivative, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), inhibited the growth of human non-small cell lung cancer (NSCLC) cells in dose- and time-dependent manners. The cytotoxicity was mediated through apoptotic cell death that began with mitochondrial membrane potential interruption and DNA damage. EMMQ caused transient elevation of p53 that assists in cytochrome c release, cleavage of downstream PARP and procaspase-3 and mitochondria-related apoptosis. The degree of apoptotic cell death depends on the status of tumor suppressor p53 of the target cells. H...
Source: Apoptosis - September 8, 2015 Category: Molecular Biology Source Type: research

Chaetocin induces endoplasmic reticulum stress response and leads to death receptor 5-dependent apoptosis in human non-small cell lung cancer cells
Abstract Epigenetic abnormalities are associated with non-small cell lung cancer (NSCLC) initiation and progression. Epigenetic drugs are being studied and in clinical trials. However, the molecular mechanism underlying the apoptosis by the epigenetic agents remains unclear. SUV39H1 is an important methyl-transferase for lysine 9 on histone H3 and usually related to gene transcriptional suppression, and chaetocin acts as the inhibitor of SUV39H1. We demonstrated here that chaetocin effectively suppressed the growth of multiple lung cancer cells through inducing apoptosis in a death receptor 5 (DR5)-dependent manne...
Source: Apoptosis - September 8, 2015 Category: Molecular Biology Source Type: research

Integral membrane protease fibroblast activation protein sensitizes fibrosarcoma to chemotherapy and alters cell death mechanisms
Abstract Fibroblast activation protein (FAP), an integral membrane serine protease, is found on fibro- and osteo-sarcoma and on myofibroblasts in epithelial carcinoma, but rarely on other adult tissue. FAP has been demonstrated to be an excellent target for tumor imaging in clinical trials, and antibodies and other FAP-targeting drugs are in development. Here we have shown that FAP overexpression increased the growth of HT1080 fibrosarcoma cells in vitro and in vivo, and found that the expression of FAP affects response to chemotherapy. When treated with doxorubicin, expression of FAP increased susceptibility to t...
Source: Apoptosis - September 5, 2015 Category: Molecular Biology Source Type: research

Serum-dependent processing of late apoptotic cells and their immunogenicity
Abstract The execution phase of apoptosis involves many processes which modify cellular molecules for an efficient and quiet elimination of the dead cell. These include exposure and secretion of “eat-me” signals, to attract phagocytes, as well as degradation of immune-stimulating cell debris. During this phase apoptotic microparticles (MPs) are released from the dying cell. The remaining cell remnant forms large late apoptotic cell-derived membranous vesicles (ACMVL) on its surface which remain attached. Phagocytosis is enhanced by cell non-autonomous factors such as complement component C1q and serum ...
Source: Apoptosis - September 4, 2015 Category: Molecular Biology Source Type: research

Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic β-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways
Abstract Lipotoxicity plays a vital role in development and progression of type 2 diabetes. Prolonged elevation of free fatty acids especially the palmitate leads to pancreatic β-cell dysfunction and apoptosis. Curcumin (diferuloylmethane), a polyphenol from the curry spice turmeric, is considered to be a broadly cytoprotective agent. The present study was designed to determine the protective effect of curcumin on palmitate-induced apoptosis in β-cells and investigate underlying mechanisms. Our results showed that curcumin improved cell viability and enhanced glucose-induced insulin secretory function in...
Source: Apoptosis - September 2, 2015 Category: Molecular Biology Source Type: research

Apoptosis induction in human breast cancer (MCF-7) cells by a novel venom l -amino acid oxidase (Rusvinoxidase) is independent of its enzymatic activity and is accompanied by caspase-7 activation and reactive oxygen species production
We report the elucidation of a mechanism of apoptosis induction in breast cancer (MCF-7) cells by an l-amino acid oxidase (LAAO), Rusvinoxidase, purified from the venom of Daboia russelii russelii. Peptide mass fingerprinting analysis of Rusvinoxidase, an acidic monomeric glycoprotein with a mass of ~57 kDa, confirmed its identity as snake venom LAAO. The enzymatic activity of Rusvinoxidase was completely abolished after two cycles of freezing and thawing; however, its cytotoxicity toward MCF-7 cells remained unaffected. Dose- and time-dependent induction of apoptosis by Rusvinoxidase on MCF-7 cells was evident from c...
Source: Apoptosis - August 28, 2015 Category: Molecular Biology Source Type: research

An epistatic effect of apaf - 1 and caspase - 9 on chlamydial infection
Abstract Chlamydia is an obligate intracellular bacterial pathogen that replicates solely within a membrane-bound vacuole termed an inclusion. Chlamydia seems to perturb multiple cellular processes of the host, such as, rearrangement of the membrane trafficking system for its intracellular multiplication, and inhibition of host cell apoptosis for persistent infection. In an attempt to clarify host factor involvement in apoptosis regulation, we found that inhibition of Caspase-9 restricted, while Apaf-1 promoted, Chlamydia pneumoniae infection in HEp-2, HeLa, and mouse epithelial fibroblast (MEF) cel...
Source: Apoptosis - August 20, 2015 Category: Molecular Biology Source Type: research

In situ allicin generation using targeted alliinase delivery for inhibition of MIA PaCa-2 cells via epigenetic changes, oxidative stress and cyclin-dependent kinase inhibitor (CDKI) expression
Abstract Allicin, an extremely active constituent of freshly crushed garlic, is produced upon reaction of substrate alliin with the enzyme alliinase (EC 4.4.1.4). Allicin has been shown to be toxic to several mammalian cells in vitro in a dose-dependent manner. In the present study this cytotoxicity was taken to advantage to develop a novel approach to cancer treatment, based on site directed generation of allicin. Alliinase was chemically conjugated to a monoclonal antibody (mAb) which was directed against a specific pancreatic cancer marker, CA19-9. After the CA19-9 mAb-alliinase conjugate was bound to targeted ...
Source: Apoptosis - August 19, 2015 Category: Molecular Biology Source Type: research

Morin mitigates acetaminophen-induced liver injury by potentiating Nrf2 regulated survival mechanism through molecular intervention in PHLPP2-Akt-Gsk3β axis
Abstract Acetaminophen (APAP) is frequently taken to relieve pain. Staggered APAP overdoses have been reported to cause acetaminophen-induced liver injury (AILI). Identification of efficacious therapeutic modalities to address complications imposed by accidental/intentional long-term APAP ingestion is needed. Morin, a plant-derived phytochemical, possesses a multitude of pharmacological properties including hepatoprotective action; however, the underlying mechanisms have been inadequately explored. Our present report demonstrates significant attenuation of APAP-mediated liver injury by morin supplementation in viv...
Source: Apoptosis - August 19, 2015 Category: Molecular Biology Source Type: research

In vitro antiproliferative, pro-apoptotic, antimetastatic and anti-inflammatory potential of 2,4-diacteylphloroglucinol (DAPG) by Pseudomonas aeruginosa strain FP10
Abstract The 2,4-diacteylphloroglucinol (DAPG), a polyketide metabolite extracted from Pseudomonas aeruginosa strain FP10, exhibited selective cytoxicity against lung (A549), breast (MDA MB-231), cervical (HeLa) and colon (HCT-15) cancer cells in differential and dose-dependent manner. The anticancer and antimetastatic activities of DAPG were mediated by the inhibition of ROS, NF-κB, Bcl-2, MMP-2, VEGF and primary inflammatory mediators such as TNF-α, IL-6, IL-1β and NO. The DAPG induced apoptosis in cancer cells by intrinsic and extrinsic pathways via the release of cytochrome-C, upregulatio...
Source: Apoptosis - August 18, 2015 Category: Molecular Biology Source Type: research

A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects
This study highlights the importance of iRGD on enhancement of cell penetration and tumor accumulation. In summary, our findings demonstrate that the novel modified Tα1 developed in this study has the potential to be used for treating breast cancer. (Source: Apoptosis)
Source: Apoptosis - August 18, 2015 Category: Molecular Biology Source Type: research

Metformin synergizes 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) combination therapy through impairing intracellular ATP production and DNA repair in breast cancer stem cells
In conclusion, our results suggest that metformin synergizes FEC sensitivity through distinct mechanism in parental breast cancer cell lines and CSCs, thus providing further evidence for the clinical relevance of metformin for the treatment of cancers. (Source: Apoptosis)
Source: Apoptosis - August 15, 2015 Category: Molecular Biology Source Type: research

Polymorphism in apoptotic BAX (-248G>A) gene but not in anti-apoptotic BCL2 (-938C>A) gene and its protein and mRNA expression are associated with cervical intraepithelial neoplasia
In conclusion, our data provide evidence that allele G carriers in the BAX-248G>A promoter SNP may influence the development of SIL. However, this genotype does not influence the SIL outcome. Additionally, we suggest a possible role of HPV infection in the inhibition of the expression of BAX protein, decreasing cell death, and favoring cervical carcinogenesis. (Source: Apoptosis)
Source: Apoptosis - August 13, 2015 Category: Molecular Biology Source Type: research

Autophagy protects meniscal cells from glucocorticoids-induced apoptosis via inositol trisphosphate receptor signaling
Abstract Intra-articular injection of glucocorticoids (GCs) has been widely used in the management of osteoarthritis and rheumatoid arthritis. Nevertheless, several studies showed that GCs had toxic effects on chondrocytes as well as synovial cells. Previously we reported the protective role of autophagy in the degeneration of meniscal tissues. However, the effects of GCs on autophagy in the meniscal cells have not been fully elucidated. To investigate whether GCs can regulate autophagy in human meniscal cells, the meniscal cells were cultured in vitro and exposed in the presence of dexamethasone. The levels of a...
Source: Apoptosis - August 11, 2015 Category: Molecular Biology Source Type: research

Novel antiapoptotic effect of TBX15: overexpression of TBX15 reduces apoptosis in cancer cells
Abstract T-box genes regulate development processes, some of these genes having also a role in cell proliferation and survival. TBX15 is a T-box transcription factor that, recently, has been proposed as a marker in prostate cancer, but its function in carcinogenesis is unknown. Here the role of TBX15 in carcinogenesis was investigated using thyroid cancer cell lines. First, using western blot analysis, we show that the expression of TBX15 was altered in thyroid cancer cells lines with respect to normal thyroid cells. Transfection of thyroid cancer cells with TBX15, in the presence or absence of camptothecin as...
Source: Apoptosis - July 28, 2015 Category: Molecular Biology Source Type: research

The miR-573/apoM/Bcl2A1-dependent signal transduction pathway is essential for hepatocyte apoptosis and hepatocarcinogenesis
Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with an increasing incidence worldwide. Apolipoprotein M (apoM) is a novel apolipoprotein that is mainly expressed in liver and kidney tissues. However, the anti-tumor properties of apoM remain largely unknown. We evaluated the anti-tumor activities and mechanisms of apoM in HCC both in vivo and in vitro. Bioinformatic analysis and luciferase reporter assay results showed that apoM was a potential target of hsa-miR-573 and was downregulated after transfection with hsa-miR-573 mimics. Overexpression of apoM suppressed migration, inva...
Source: Apoptosis - July 23, 2015 Category: Molecular Biology Source Type: research

Evidence for anti-apoptotic roles of proteasome activator 28γ via inhibiting caspase activity
In this study we demonstrate a correlation between cellular PA28γ levels and the sensitivity of cells towards apoptosis in different cellular contexts thereby confirming a role of proteasome activator PA28γ as an anti-apoptotic regulator. We investigated the anti-apoptotic role of PA28γ upon UV-C stimulation in B8 mouse fibroblasts stably overexpressing the PA28γ-encoding PSME3 gene and upon butyrate-induced apoptosis in human HT29 adenocarcinoma cells with silenced PSME3 gene. Interestingly, our results demonstrate that PA28γ has a strong influence on different apoptotic hallmarks, especially...
Source: Apoptosis - July 23, 2015 Category: Molecular Biology Source Type: research

Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling
This study aimed to evaluate the chondroprotective effect and underlying mechanisms of BBR on sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis and surgically-induced rat OA model. The in vitro results revealed that BBR suppressed SNP-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, down-regulated expressions of inducible nitric oxide synthase (iNOS) and caspase-3, and up-regulated Bcl-2/Bax ratio and Type II collagen (Col II) at protein levels, which were accompanied by increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased phosphorylation of...
Source: Apoptosis - July 17, 2015 Category: Molecular Biology Source Type: research

LYG-202 exerts antitumor effect on PI3K/Akt signaling pathway in human breast cancer cells
In this study, we aimed to investigate the antitumor effect of LYG-202, a newly synthesized piperazine-substituted derivative of flavonoid on human breast cancer cells and illustrate the potential mechanisms. LYG-202 induced apoptosis in MCF-7, MDA-MB-231 and MDA-MB-435 cells. LYG-202 triggered the activation of mitochondrial apoptotic pathway through multiple steps: increasing Bax/Bcl-2 ratio, decreasing mitochondrial membrane potential (ΔΨ m ), activating caspase-9 and caspase-3, inducing cleavage of poly(ADP-ribose) polymerase, cytochrome c release and apoptosis-inducing fac...
Source: Apoptosis - July 8, 2015 Category: Molecular Biology Source Type: research

A soluble receptor for advanced glycation end-products inhibits myocardial apoptosis induced by ischemia/reperfusion via the JAK2/STAT3 pathway
Abstract sRAGE can protect cardiomyocytes from apoptosis induced by ischemia/reperfusion (I/R). However, the signaling mechanisms in cardioprotection by sRAGE are currently unknown. We investigated the cardioprotective effect and potential molecular mechanisms of sRAGE inhibition on apoptosis in the mouse myocardial I/R as an in vivo model and neonatal rat cardiomyocyte subjected to ischemic buffer as an in vitro model. Cardiac function and myocardial infarct size following by I/R were evaluated with echocardiography and Evans blue/2,3,5-triphenyltetrazolium chloride. Apoptosis was detected by TUNEL staining and ...
Source: Apoptosis - June 24, 2015 Category: Molecular Biology Source Type: research

Tunicamycin promotes apoptosis in leukemia cells through ROS generation and downregulation of survivin expression
Abstract Tunicamycin (TN), one of the endoplasmic reticulum stress inducers, has been reported to inhibit tumor cell growth and exhibit anticarcinogenic activity. However, the mechanism by which TN initiates apoptosis remains poorly understood. In the present study, we investigated the effect of TN on the apoptotic pathway in U937 cells. We show that TN induces apoptosis in association with caspase-3 activation, generation of reactive oxygen species (ROS), and downregulation of survivin expression. P38 MAPK (mitogen-activated protein kinase) and the generation of ROS signaling pathway play crucial roles in TN-ind...
Source: Apoptosis - June 24, 2015 Category: Molecular Biology Source Type: research

Notch3/Akt signaling contributes to OSM-induced protection against cardiac ischemia/reperfusion injury
Abstract Oncostatin M (OSM) exhibits many unique biological activities by activating the Oβ receptor. However, its role in myocardial ischemia/reperfusion injury (I/R injury) in mice remains unknown. We investigated whether Notch3/Akt signaling is involved in the regulation of OSM-induced protection against cardiac I/R injury. The effects of OSM were assessed in mice that underwent myocardial I/R injury by OSM treatment or by genetic deficiency of the OSM receptor Oβ. We investigated its effects on cardiomyocyte apoptosis and mitochondrial biogenesis and whether Notch3/Akt signaling was involved in the r...
Source: Apoptosis - June 21, 2015 Category: Molecular Biology Source Type: research

Multifaceted role of prohibitin in cell survival and apoptosis
Abstract Human eukaryotic prohibitin (prohibitin-1 and prohibitin-2) is a membrane protein with different cellular localizations. It is involved in multiple cellular functions, including energy metabolism, proliferation, apoptosis, and senescence. The subcellular localization of prohibitin may determine its functions. Membrane prohibitin regulate the cellular signaling of membrane transport, nuclear prohibitin control transcription activation and the cell cycle, and mitochondrial prohibitin complex stabilize the mitochondrial genome and modulate mitochondrial dynamics, mitochondrial morphology, mitochondrial bioge...
Source: Apoptosis - June 20, 2015 Category: Molecular Biology Source Type: research

Protective effect of low dose gadolinium chloride against isoproterenol-induced myocardial injury in rat
In conclusion, this study demonstrates for the first time that GdCl3 protects myocardium against ISO-induced cell apoptosis through, at least partly, serving as a scavenger of AA, therefore abolishing its downstream activation of the death receptor regulated apoptosis pathway. (Source: Apoptosis)
Source: Apoptosis - June 19, 2015 Category: Molecular Biology Source Type: research

Critical role of the α1-Na + , K + -ATPase subunit in insensitivity of rodent cells to cytotoxic action of ouabain
Abstract In rodents, ubiquitous α1-Na+, K+-ATPase is inhibited by ouabain and other cardiotonic steroids (CTS) at ~103-fold higher concentrations than those effective in other mammals. To examine the specific roles of the CTS-sensitive α1S- and CTS-resistant α1R-Na+, K+-ATPase isoforms, we compared the effects of ouabain on intracellular Na+ and K+ content, cell survival, and mitogen-activated protein kinases (MAPK) in human and rat vascular smooth muscle cells (HASMC and RASMC), human and rat endothelial cells (HUVEC and RAEC), and human and rat brain astrocytes. 6-h exposure of HASMC and HUVEC ...
Source: Apoptosis - June 12, 2015 Category: Molecular Biology Source Type: research

Activation of endoplasmic reticulum stress is involved in the activity of icariin against human lung adenocarcinoma cells
In this study, we investigated the anticancer activity of icariin (ICA) against human lung adenocarcinoma cells in vitro and in vivo and explored the role of endoplasmic reticulum (ER) stress (ERS) signaling in this process. ICA treatment resulted in a dose- and time-dependent decrease in the viability of human lung adenocarcinoma A549 cells. Additionally, ICA exhibited potent anticancer activity, as evidenced by reductions in A549 cell adhesion, migration and intracellular glutathione (GSH) levels and increases in the apoptotic index, Caspase 3 activity, and reactive oxygen species. Furthermore, ICA treatment increased th...
Source: Apoptosis - June 6, 2015 Category: Molecular Biology Source Type: research

PUMA-mediated mitochondrial apoptotic disruption by hypoxic postconditioning
Abstract Postconditioning can reduce ischemia–reperfusion (I/R)-induced cardiomyocyte apoptosis by targeting mitochondria. p53 upregulated modulator of apoptosis (PUMA) is involved in lethal I/R injury. Here, we hypothesized that postconditioning might inhibit mitochondrial pathway-mediated cardiomyocyte apoptosis by controlling PUMA expression. The cultured neonatal rat cardiomyocytes underwent 3 h of hypoxia and 3 h of reoxygenation. Postconditioning consisted of three cycles of 5 min reoxygenation and 5 min hypoxia after prolonged hypoxia. Hypoxic postconditioning reduced the levels of...
Source: Apoptosis - June 5, 2015 Category: Molecular Biology Source Type: research

Inflammation-induced radioresistance is mediated by ROS-dependent inactivation of protein phosphatase 1 in non-small cell lung cancer cells
Abstract Inflammation plays a pivotal role in modulating the radiation responsiveness of tumors. We determined that an inflammation response prior to irradiation contributes to radiotherapy resistance in non-small cell lung cancer (NSCLC) cells. In the clonogenic survival assay, activation of the inflammation response by lipopolysaccharide (LPS) decreased the degree of radiosensitivity in NCI-H460 cells (relatively radiosensitive cells), but had no effect in A549 cells (relatively radioresistant cells). LPS-induced radioresistance of NCI-H460 cells was also confirmed with a xenograft mouse model. The radioresistan...
Source: Apoptosis - June 2, 2015 Category: Molecular Biology Source Type: research

Alantolactone induces G1 phase arrest and apoptosis of multiple myeloma cells and overcomes bortezomib resistance
Abstract Several sesquiterpene lactones have been extracted and demonstrated to exert various pharmacological functions in a variety of cancers. Here, we investigated anti-tumor effect of alantolactone, an allergenic sesquiterpene lactone, on human multiple myeloma (MM) and showed alantolactone inhibited growth of MM cells, both in the presence or absence of bone marrow (BM)-derived stromal cells (HS-5), and subsequent G1 phase arrest, and apoptosis as demonstrated by increased Annexin-V/7-AAD binding, caspase-3 or caspase-9 activation and down-modulation of activation of extracellular signal-regulated kinases...
Source: Apoptosis - June 2, 2015 Category: Molecular Biology Source Type: research

Fructose induces mitochondrial dysfunction and triggers apoptosis in skeletal muscle cells by provoking oxidative stress
Abstract Mitochondrial dysfunction in skeletal muscle has been implicated in the development of insulin resistance, a major characteristic of type 2 diabetes. There is evidence that oxidative stress results from the increased production of reactive oxygen species and reactive nitrogen species leads to mitochondrial dysfunction, tissue damage, insulin resistance, and other complications observed in type 2 diabetes. It has been suggested that intake of high fructose contributes to insulin resistance and other metabolic disturbances. However, there is limited information about the direct effect of fructose on th...
Source: Apoptosis - May 29, 2015 Category: Molecular Biology Source Type: research

Loss of α(E)-catenin promotes Fas mediated apoptosis in tubular epithelial cells
In this study, cells were challenged with nephrotoxicant cisplatin to induce AKI. A ~5.5-fold increase in Fas expression in C2 (stable α(E)-catenin knockdown) relative to NT3 (non-targeted control) cells was seen. Increased caspase-8 and -9 activation was induced by cisplatin in C2 as compared to NT3 cells. In addition, decreased Bcl-2 expression and increased BID cleavage and cytochrome C release were detected in C2 cells after cisplatin challenge. Treating the cells with cisplatin, in combination with a Bcl-2 inhibitor, decreased the viability of NT3 cells to the same level as C2 cells after cisplatin. Furthermore,...
Source: Apoptosis - May 29, 2015 Category: Molecular Biology Source Type: research

Microglia activation and interaction with neuronal cells in a biochemical model of mevalonate kinase deficiency
Abstract Mevalonate kinase deficiency is a rare disease whose worst manifestation, characterised by severe neurologic impairment, is called mevalonic aciduria. The progressive neuronal loss associated to cell death can be studied in vitro with a simplified model based on a biochemical block of the mevalonate pathway and a subsequent inflammatory trigger. The aim of this study was to evaluate the effect of the mevalonate blocking on glial cells (BV-2) and the following effects on neuronal cells (SH-SY5Y) when the two populations were cultured together. To better understand the cross-talk between glial and neuronal ...
Source: Apoptosis - May 24, 2015 Category: Molecular Biology Source Type: research

Thymosin alpha 1 suppresses proliferation and induces apoptosis in breast cancer cells through PTEN-mediated inhibition of PI3K/Akt/mTOR signaling pathway
Abstract Thymosin alpha 1 (Tα1), an immunoactive peptide, has been shown to inhibit cell proliferation and induce apoptosis in human leukemia, non-small cell lung cancer, melanoma, and other human cancers. However, the response and molecular mechanism of breast cancer cells exposed to Tα1 remain unclear. PTEN, a tumor suppressor gene, is frequently mutated in a variety of human cancers. In the present study, we aimed to investigate the biological roles of PTEN in the growth inhibition of human breast cancer cells exposed to Tα1. Using wild-type and mutant PTEN-expressing cells, we found a strong...
Source: Apoptosis - May 23, 2015 Category: Molecular Biology Source Type: research

Carnitine transporter CT2 (SLC22A16) is over-expressed in acute myeloid leukemia (AML) and target knockdown reduces growth and viability of AML cells
We examined the expression of the known plasma membrane carnitine transporters, OCTN1, OCTN2, and CT2 in AML cell lines and primary AML samples and compared expression to normal hematopoietic cells. Of the three carnitine transporters, CT2 demonstrated the greatest differential expression between AML and normal cells. Using shRNA, we knocked down CT2 and demonstrated that target knockdown impaired the function of the transporter. In addition, knockdown of CT2 reduced the growth and viability of AML cells with high expression of CT2 (OCI-AML2 and HL60), but not low expression. CT2 knockdown reduced basal oxygen consumption ...
Source: Apoptosis - May 22, 2015 Category: Molecular Biology Source Type: research

Apoptosis in mammalian oocytes: a review
Abstract Apoptosis causes elimination of more than 99 % of germ cells from cohort of ovary through follicular atresia. Less than 1 % of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3′,5′-cyclic monophosphate and guanosine 3′,5′-c...
Source: Apoptosis - May 10, 2015 Category: Molecular Biology Source Type: research

Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions
Abstract Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but the sequence in which these processes occur remains a matter of debate. Here we investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa, in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI 166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed significant increases in the protein expression of p27, p21, phospho-eukaryotic elongation factor 4E-binding protein 1, and phospho-p70 S6 rib...
Source: Apoptosis - May 8, 2015 Category: Molecular Biology Source Type: research

Regulation of viability, differentiation and death of human melanoma cells carrying neural stem cell biomarkers: a possibility for neural trans-differentiation
Abstract During embryonic development, melanoblasts, the precursors of melanocytes, emerge from a subpopulation of the neural crest stem cells and migrate to colonize skin. Melanomas arise during melanoblast differentiation into melanocytes and from young proliferating melanocytes through somatic mutagenesis and epigenetic regulations. In the present study, we used several human melanoma cell lines from the sequential phases of melanoma development (radial growth phase, vertical growth phase and metastatic phase) to compare: (i) the frequency and efficiency of the induction of cell death via apoptosis and necropto...
Source: Apoptosis - May 8, 2015 Category: Molecular Biology Source Type: research

Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells
This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key ro...
Source: Apoptosis - May 3, 2015 Category: Molecular Biology Source Type: research

AutomiRDB: a web resource connecting microRNAs and autophagy in cancer
(Source: Apoptosis)
Source: Apoptosis - May 1, 2015 Category: Molecular Biology Source Type: research

Protective effect of berberine against myocardial ischemia reperfusion injury: role of Notch1/Hes1-PTEN/Akt signaling
In this study, male Sprague–Dawley rats were exposed to BBR treatment (200 mg/kg/d) for 2 weeks and then subjected to MI/RI. BBR significantly improved cardiac function recovery and decreased myocardial apoptosis, infarct size, serum creatine kinase and lactate dehydrogenase levels. Furthermore, in cultured H9c2 cardiomyocytes, BBR (50 μmol/L) attenuated simulated ischemia/reperfusion-induced myocardial apoptosis. Both in vivo and in vitro study showed that BBR treatment up-regulates Notch1 intracellular domain, Hes1, Bcl-2 expression and p-Akt/Akt ratio, down-regulates Bax Caspase-3 and cleaved Cas...
Source: Apoptosis - April 12, 2015 Category: Molecular Biology Source Type: research

Antineoplastic impact of leishmanial sphingolipid in tumour growth with regulation of angiogenic event and inflammatory response
Abstract Very often conventional therapy, i.e. chemotherapeutic treatment, develops resistance in cancer cells and fails to be effective against disease states. An alternative strategy or a new entity may resolve the problem. Interestingly, the microbial world has begun to be explored in medicinal research as a potential new source to deliver bio-active molecules such as sphingolipids for efficacious cancer treatment. A sphingolipid of microbial origin, especially from Leishmania donovani (LSPL), is a novel entity which may exert anti-cancer activity by regulating cellular growth. The present study reveals that a...
Source: Apoptosis - April 12, 2015 Category: Molecular Biology Source Type: research

Apoptin interacts with and regulates the activity of protein kinase C beta in cancer cells
Abstract Apoptin, the VP3 protein from chicken anaemia virus (CAV), induces tumour cell-specific cell death and represents a potential future anti-cancer therapeutic. In tumour but not in normal cells, Apoptin is phosphorylated and translocates to the nucleus, enabling its cytotoxic activity. Recently, the β isozyme of protein kinase C (PKCβ) was shown to phosphorylate Apoptin in multiple myeloma cell lines. However, the exact mechanism and nature of interaction between PKCβ and Apoptin remain unclear. Here we investigated the physical and functional link between PKCβ and CAV-Apoptin as well a...
Source: Apoptosis - April 12, 2015 Category: Molecular Biology Source Type: research

Phenazine-1-carboxamide (PCN) from Pseudomonas sp. strain PUP6 selectively induced apoptosis in lung (A549) and breast (MDA MB-231) cancer cells by inhibition of antiapoptotic Bcl-2 family proteins
Abstract Phenazine-1-carboxamide (PCN), a naturally occurring simple phenazine derivative isolated from Pseudomonas sp. strain PUP6, exhibited selective cytotoxic activity against lung (A549) and breast (MDA-MB-231) cancer cell lines in differential and dose-dependent manner compared to normal peripheral blood mononuclear cells. PCN-treated cancer cells showed the induction of apoptosis as evidenced by the release of low level of LDH, morphological characteristics, production of reactive oxygen species, loss of mitochondrial membrane potential (ΔΨm) and induction of caspase-3. At molecular level, PCN in...
Source: Apoptosis - April 12, 2015 Category: Molecular Biology Source Type: research

Mitochondrial DNA damage by bleomycin induces AML cell death
Abstract Mitochondria contain multiple copies of their own 16.6 kb circular genome. To explore the impact of mitochondrial DNA (mtDNA) damage on mitochondrial (mt) function and viability of AML cells, we screened a panel of DNA damaging chemotherapeutic agents to identify drugs that could damage mtDNA. We identified bleomycin as an agent that damaged mtDNA in AML cells at concentrations that induced cell death. Bleomycin also induced mtDNA damage in primary AML samples. Consistent with the observed mtDNA damage, bleomycin reduced mt mass and basal oxygen consumption in AML cells. We also demonstrated that th...
Source: Apoptosis - April 12, 2015 Category: Molecular Biology Source Type: research

Combination of erlotinib and EGCG induces apoptosis of head and neck cancers through posttranscriptional regulation of Bim and Bcl-2
Abstract Combinatorial approaches using two or more compounds are gaining increasing attention for cancer therapy. We have previously reported that the combination of the EGFR-TKI erlotinib and epigallocatechin-3-gallate (EGCG) exhibited synergistic chemopreventive effects in head and neck cancers by inducing the expression of Bim, p21, p27, and by inhibiting the phosphorylation of ERK and AKT and expression of Bcl-2. In the current study, we further investigated the mechanism of regulation of Bim, Bcl-2, p21 and p27, and their role in apoptosis. shRNA-mediated silencing of Bim significantly inhibited apoptosis in...
Source: Apoptosis - April 10, 2015 Category: Molecular Biology Source Type: research

A novel cisplatin mediated apoptosis pathway is associated with acid sphingomyelinase and FAS proapoptotic protein activation in ovarian cancer
We report here that these DNA-damaging agents, particularly cisplatin, induce apoptosis through plasma membrane disruption, triggering FAS death receptor via mitochondrial (intrinsic) pathways. Our objectives were to: quantify the composition of membrane metabolites; and determine the potential involvement of acid sphingomyelinase (ASMase) in the FAS-mediated apoptosis in ovarian cancer after cisplatin treatment. The resulting analysis revealed enhanced apoptosis as measured by: increased phosphocholine, and glycerophosphocholine; elevated cellular energetics; and phosphocreatine and nucleoside triphosphate concentrations....
Source: Apoptosis - April 7, 2015 Category: Molecular Biology Source Type: research

Mycobacterium tuberculosis effectors interfering host apoptosis signaling
Abstract Tuberculosis remains a serious human public health concern. The coevolution between its pathogen Mycobacterium tuberculosis and human host complicated the way to prevent and cure TB. Apoptosis plays subtle role in this interaction. The pathogen endeavors to manipulate the apoptosis via diverse effectors targeting key signaling nodes. In this paper, we summarized the effectors pathogen used to subvert the apoptosis, such as LpqH, ESAT-6/CFP-10, LAMs. The interplay between different forms of cell deaths, such as apoptosis, autophagy, necrosis, is also discussed with a focus on the modes of action of eff...
Source: Apoptosis - April 3, 2015 Category: Molecular Biology Source Type: research

The synergistic effect of BCR signaling inhibitors combined with an HDAC inhibitor on cell death in a mantle cell lymphoma cell line
Abstract Mantle cell lymphoma (MCL) is a B cell malignancy characterized by aberrant expression of cyclin D1 due to a t(11;14) translocation. MCL is refractory to conventional chemotherapy, and treatment remains challenging. We investigated the efficacy of the histone deacetylase (HDAC) inhibitor vorinostat combined with one of several B-cell receptor (BCR) signaling inhibitors on MCL cell death and the underlying mechanisms, using MCL cell lines. The Bruton’s tyrosine kinase inhibitor PCI-32765 and the spleen tyrosine kinase inhibitor R406 showed synergistic effects with vorinostat on growth inhibition. Tre...
Source: Apoptosis - April 3, 2015 Category: Molecular Biology Source Type: research

Select microtubule inhibitors increase lysosome acidity and promote lysosomal disruption in acute myeloid leukemia (AML) cells
Abstract To identify new biological vulnerabilities in acute myeloid leukemia, we screened a library of natural products for compounds cytotoxic to TEX leukemia cells. This screen identified the novel small molecule Deoxysappanone B 7,4′ dimethyl ether (Deox B 7,4), which possessed nanomolar anti-leukemic activity. To determine the anti-leukemic mechanism of action of Deox B 7,4, we conducted a genome-wide screen in Saccharomyces cerevisiae and identified enrichment of genes related to mitotic cell cycle as well as vacuolar acidification, therefore pointing to microtubules and vacuolar (V)-ATPase as potentia...
Source: Apoptosis - April 2, 2015 Category: Molecular Biology Source Type: research

Combined blockade of angiotensin II and prorenin receptors ameliorates podocytic apoptosis induced by IgA-activated mesangial cells
In this study, we examine the role of podocytic angiotensin II receptor subtype 1 (AT1R) and prorenin receptor (PRR) in podocytic apoptosis in IgAN. Polymeric IgA (pIgA) was isolated from patients with IgAN and healthy controls. Conditioned media were prepared from growth arrested human mesangial cells (HMC) incubated with pIgA from patients with IgAN (IgA-HMC media) or healthy controls (Ctl-HMC media). A human podocyte cell line was used as a model to examine the regulation of the expression of AT1R, PRR, TNF-α and CTGF by IgA-HMC media. Podocytic nephrin expression, annexin V binding and caspase 3 activity were use...
Source: Apoptosis - March 26, 2015 Category: Molecular Biology Source Type: research