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Blockade of autophagy enhances proapoptotic potential of BI-69A11, a novel Akt inhibitor, in colon carcinoma.
Abstract BI-69A11, novel Akt inhibitor, is currently drawing much attention due to its intriguing effect in inducing apoptosis in melanoma, breast, prostate and colon cancer. However, earlier reports reveal that PI3K/Akt/ mTOR inhibitors promote autophagy at the early stage as a survival mechanism that might affect its apoptotic potential. It is necessary to investigate whether BI-69A11 mediated apoptosis is associated with autophagy for enhancing its therapeutic efficacy. Here, we found that BI-69A11 induced autophagy at earlier time point through the inhibition of Akt/mTOR/p70S6kinase pathway. Dose-dependent and...
Source: European Journal of Pharmacology - August 22, 2015 Category: Drugs & Pharmacology Authors: Pal I, Parida S, Prashanth Kumar BN, Banik P, Kumar Dey K, Chakraborty S, Bhutia SK, Mandal M Tags: Eur J Pharmacol Source Type: research

Autocrine secretion of 15d‐PGJ2 mediates simvastatin‐induced apoptotic burst in human metastatic melanoma cells
Conclusions and ImplicationsWe characterized simvastatin‐induced activation of the 15d‐PGJ2/FABP5 signalling cascades, which triggered an apoptotic burst in melanoma cells but did not affect primary human melanocytes. These data support the rationale for the pharmacological targeting of 15d‐PGJ2 in metastatic melanoma.
Source: British Journal of Pharmacology - December 1, 2014 Category: Drugs & Pharmacology Authors: Christine Wasinger, Martin Künzl, Christoph Minichsdorfer, Christoph Höller, Maria Zellner, Martin Hohenegger Tags: RESEARCH PAPER Source Type: research

Autocrine secretion of 15d‐PGJ2 mediates simvastatin induced apoptotic burst in human metastatic melanoma cells
ConclusionWe here delineate simvastatin induced activation of the 15d‐PGJ2/FABP5 signalling cascades, which trigger an apoptotic burst in melanoma cells, while primary human melanocytes were unaffected. These data support new rational ground for pharmacological targeting of 15d‐PGJ2 in metastatic melanoma.
Source: British Journal of Pharmacology - August 4, 2014 Category: Drugs & Pharmacology Authors: Christine Wasinger, Martin Künzl, Christoph Minichsdorfer, Christoph Höller, Maria Zellner, Martin Hohenegger Tags: Research Paper Source Type: research

Inhibition of Cancer Cell Growth by GRP78 siRNA Lipoplex via Activation of Unfolded Protein Response.
Abstract Proteasome inhibitors are a novel class of molecular-targeted anti-cancer drugs that suppress the degradation of malfolded proteins, trigger endoplasmic reticulum (ER) stress, and activate apoptosis signals. Glucose-regulated protein 78 (GRP78), a major ER chaperone, is one of the most important molecules for transduction of unfolded protein response (UPR) signals. In accordance with past findings that expression of GRP78 is elevated in cancer cells and helps to resist stress-induced apoptosis, GRP78 knockdown could be effective in anticancer therapy. We tested this hypothesis and found that transfection ...
Source: Biological and Pharmaceutical Bulletin - April 6, 2014 Category: Drugs & Pharmacology Authors: Matsumura K, Sakai C, Kawakami S, Yamashita F, Hashida M Tags: Biol Pharm Bull Source Type: research

Anti-melanogenic effects of δ-tocotrienol are associated with tyrosinase-related proteins and MAPK signaling pathway in B16 melanoma cells
This study aimed to elucidate the mechanism involved in the anti-melanogenic effects of δ-tocotrienol (δT3) in B16 melanoma cells. Results showed that at 20μM of δT3 significantly inhibited melanin formation and ROS generation. Treatment with δT3 also effectively suppressed the expression of melanogenesis-related proteins, including MC1R, MITF, TYRP-1, and TYRP-2. More importantly, we observed that the mitogen-activated protein kinase (MAPK) pathway was involved in mediating δT3's inhibitory effect against melanin production. Specifically, δT3 treatment markedly induced the activation of extracellular signal-regulat...
Source: Phytomedicine - March 27, 2014 Category: Drugs & Pharmacology Authors: Lean-Teik Ng, Liang-Tzung Lin, Chiu-Lan Chen, Hsiu-Wen Chen, Shu-Jing Wu, Chun-Ching Lin Tags: Oncology and Hematology Source Type: research

Systemic delivery of small interfering RNA by use of targeted polycation liposomes for cancer therapy.
Abstract Novel polycation liposomes decorated with cyclic(Cys-Arg-Gly-Asp-D-Phe) peptide (cyclicRGD)-polyethylene glycol (PEG) (RGD-PEG-polycation liposomes (PCL)) were previously developed for cancer therapy based on RNA interference. Here, we demonstrate the in vivo delivery of small interfering RNA (siRNA) to tumors by use of RGD-PEG-PCL in B16F10 melanoma-bearing mice. Pharmacokinetic data obtained by positron emission tomography showed that cholesterol-conjugated siRNA formulated in RGD-PEG-PCL markedly accumulated in the tumors. Delivered by RGD-PEG-PCL, a therapeutic cocktail of siRNAs composed of cholester...
Source: Biological and Pharmaceutical Bulletin - February 10, 2013 Category: Drugs & Pharmacology Authors: Kenjo E, Asai T, Yonenaga N, Ando H, Ishii T, Hatanaka K, Shimizu K, Urita Y, Dewa T, Nango M, Tsukada H, Oku N Tags: Biol Pharm Bull Source Type: research

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