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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(Institute of Cancer Research) A drug used to treat breast and ovarian cancer can extend the lives of some men with prostate cancer and should become a new standard treatment for the disease, concludes a major trial which is set to change clinical practice.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Andrzej Malinowski High levels of miRNA-103/107 are associated with poor outcomes in the case of breast cancer patients. MiRNA-103/107-DICER axis may be one of the key regulators of cancer aggressiveness. MiRNA-103/107 expression levels have never been related to patients’ clinicopathological data in epithelial ovarian cancer. We aimed to assess miRNA-103/107 expression levels in high grade serous ovarian cancer tissues. Expression levels of both miRNAs were related to the clinicopathological features and survival. We also evaluated expression levels of miRNA-103/107 and DICER in selected ovarian cancer ce...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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Source: Journal of Assisted Reproduction and Genetics - Category: Reproduction Medicine Source Type: research
AbstractPurposeTo determine the longitudinal impact of adjuvant chemotherapy and tamoxifen-only treatments on the reproductive potential of women with breast cancer by using a sensitive ovarian reserve marker anti-Mullerian hormone (AMH) as a surrogate.MethodsOne-hundred-and-forty-two women with a primary diagnosis of breast cancer were prospectively followed with serum AMH assessments before the initiation, and 12, 18 and 24  months after the completion of adjuvant chemotherapy or the start of tamoxifen-only treatment. The chemotherapy regimens were classified into Anthracycline-Cyclophosphamide-based (AC-based) and ...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
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Source: Diagnostic Pathology - Category: Pathology Authors: Tags: Case Report Source Type: research
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Source: Journal of Cancer Research and Therapeutics - Category: Cancer & Oncology Authors: Source Type: research
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Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Authors: Hwang KT, Kim MJ, Chu AJ, Park JH, Kim J, Lee JY, Choi IS, Park JH, Chang JH, Hwang KR Abstract Multiple primary malignancies are defined as the presence of more than one malignant neoplasm with a distinct histology occurring at different sites in the same individual. They are classified as synchronous or metachronous according to the diagnostic time interval of different malignancies. Diagnosis of multiple primary malignancies should avoid misclassification from multifocal/multicentric tumors or recurrent/metastatic lesions. In multiple primary malignancies, with increase in the number of primary tumors, ...
Source: Journal of Breast Cancer - Category: Cancer & Oncology Tags: J Breast Cancer Source Type: research
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Source: Advances in Medical Sciences - Category: Biomedical Science Authors: Tags: Adv Med Sci Source Type: research
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