Microtubule-stabilizing properties of the avocado-derived toxins (+)-( R )-persin and (+)-( R )-tetrahydropersin in cancer cells and activity of related synthetic analogs

Summary The avocado toxin (+)-R-persin (persin) is active at low micromolar concentrations against breast cancer cells and synergizes with the estrogen receptor modulator 4-hydroxytamoxifen. Previous studies in the estrogen receptor-positive breast cancer cell line MCF-7 indicate that persin acts as a microtubule-stabilizing agent. In the present study, we further characterize the properties of persin and several new synthetic analogues in human ovarian cancer cells. Persin and tetrahydropersin cause G2M cell cycle arrest and increase intracellular microtubule polymerization. One analog (4-nitrophenyl)-deshydroxypersin prevents cell proliferation and blocks cells in G1 of the cell cycle rather than G2M, suggesting an additional mode of action of these compounds independent of microtubules. Persin can synergize with other microtubule-stabilizing agents, and is active against cancer cells that overexpress the P-glycoprotein drug efflux pump. Evidence from Flutax-1 competition experiments suggests that while the persin binding site on β-tubulin overlaps the classical taxoid site where paclitaxel and epothilone bind, persin retains activity in cell lines with single amino acid mutations that affect these other taxoid site ligands. This implies the existence of a unique binding location for persin at the taxoid site.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: December 2019Source: Materials Science and Engineering: C, Volume 105Author(s): Rebeca T. Steipel, Matthew D. Gallovic, Cole J. Batty, Eric M. Bachelder, Kristy M. AinslieAbstractAlso known as electrospray, electrohydrodynamic atomization has been used extensively in the last 15 years to develop polymer-based particles for drug delivery in cell and animal models. More recently, novel core-shell, multi-axial, and other electrospray particles have been developed from an array of polymers for a variety of biomedical applications. This review focuses on electrospray as a novel method of particle fabrication...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research
In conclusion, the present study proposes a simple and effective strategy for identifying genes involved in chemoresistance and predicting their potential functional roles, which may guide subsequent experimental studies. PMID: 31402953 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Cancer cells abuse signals used elsewhere in normal mammalian biochemistry to prevent immune cells from destroying other cells, such as CD47. Interfering in these "don't eat me" signals has produced significant gains in the development of effective cancer therapies that can target multiple types of cancer. Here, researchers describe a newly discovered "don't eat me" signal, CD24, that should allow this class of cancer therapy to be expanded to target cancers that have proved resilient to existing implementations. This and related lines of work that lead to more general anti-cancer platforms are one of t...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Publication date: Available online 11 June 2019Source: Reproductive BioMedicine OnlineAuthor(s): KE Palinska-Rudzka, T Ghobara, N Parsons, J Milner, G Lockwood, GM HartshorneAbstractResearch questionAn important discussion point before chemotherapy is ovarian toxicity, a side-effect that profoundly affects young women with cancer. Their quality of life after successful treatment, including the ability to conceive, is a major concern. We asked whether serum anti-Müllerian hormone (AMH) measurements before chemotherapy for two most common malignancies are predictive of long-term changes in ovarian reserve?DesignA prospe...
Source: Reproductive BioMedicine Online - Category: Reproduction Medicine Source Type: research
Conclusions: The results contribute to close the knowledge gap concerning the budgetary consequences due to genetic risk classification. A rising demand leads to additional costs especially due to costs for genetic analysis. The model indicates budget shifts with cost savings due to breast and ovarian cancer treatment in the scenario of rising demands. PMID: 31394049 [PubMed - as supplied by publisher]
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
Inherited pathogenic variants in BRCA1 and BRCA2 are the most common causes of hereditary breast and ovarian cancer (HBOC). The risk of developing breast cancer by age 80 in women carrying a BRCA1 pathogenic vari...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Research article Source Type: research
Conclusions: PFKFB2 is a novel target whose inhibition can enhance the effect of paclitaxel-based primary chemotherapy upon ovarian and breast cancers retaining wtTP53. PMID: 31391192 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Abstract Olaparib (OLA) is a poly ADP ribose polymerase (PARP) inhibitor approved for germline BRCA-mutated (gBRCAm) advanced ovarian cancer and breast cancer. Low oral bioavailability of this drug requires increase in the dose and frequency causing haematological toxicity in the patients. The purpose of this study is to prepare different nano-formulations of OLA lipospheres (LP) by melt dispersion and nano-suspensions (NSP) by solvent evaporation (SE) and wet milling (WM) techniques and compare oral bioavailability of these formulations. Size of the nano-formulations OLA-LP, OLA-NSPSE and OLA-NSPWM were found to ...
Source: AAPS PharmSciTech - Category: Drugs & Pharmacology Authors: Tags: AAPS PharmSciTech Source Type: research
We presented the expressions of each member in miR-200 family in 15 types of cancer by boxplot, and analyzed the correlation among the members of miR-200 family by Spearman method. Different subgroup analyses were then performed based on the correlation among the members of miR-200 family, and the publication bias was assessed using the funnel plot of the Egger bias indicator test. RESULTS: Of 36 articles, including 15 tumor types and 4644 patients were included to perform meta-analysis. It was found that miR-200 family members can be used as independent protective factors in patients with various tumors but the miR-2...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
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