Withaferin A, a steroidal lactone from Withania somnifera, induces mitotic catastrophe and growth arrest in prostate cancer cells
Roy RV, Suman S, Das TP, Luevano JE, Damodaran C
Journal of natural products · 75 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- National Cancer Institute
- Government
- NCI NIH HHS
- Grants
- National Cancer Institute (R01 CA185972); National Cancer Institute (R01CA138797); National Cancer Institute (R01 CA140605)
Based on 2 listed funder(s).
Publication
- Published
- 2013-09-30 · J Nat Prod · vol. 76 · issue 10 · pp. 1909–1915
- Publisher
- American Chemical Society
- Cited
- 101 citations · more than 100% of similar papers · 27.3× the field average
- Impact
- Top 10% most cited in its field
- References
- 36 works
- Access
- Open access (repository copy)
- Research areas
- Phytochemicals and Medicinal Plants · PARP inhibition in cancer therapy · Cell death mechanisms and regulation
- Keywords
- Withaferin A, Prostate cancer, Mitotic catastrophe, Cancer research, Cell cycle, Cell cycle checkpoint, Mitosis, Cell growth, Cancer cell, Cancer, Cyclin-dependent kinase 1, Biology, Withania somnifera, Chemistry, Medicine, Internal medicine, Cell biology, Biochemistry, Pathology
- MeSH
- humans, withania, prostatic neoplasms, cdc2 protein kinase, cyclins, histones, cell cycle, cell division, mitosis, g2 phase, apoptosis, molecular structure, male, tumor suppressor protein p53, cyclin-dependent kinase inhibitor p21, withanolides, protein serine-threonine kinases
5 authors
From US
- Ram Vinod RoyTexas Tech University; The University of Texas at El Paso; Texas Tech University Health Sciences Center
- Suman SumanTexas Tech University; Texas Tech University Health Sciences Center
- Trinath Prasad DasTexas Tech University; Texas Tech University Health Sciences Center
- Joe E. LuevanoTexas Tech University; Texas Tech University Health Sciences Center
- Chendil Damodaran · correspondingTexas Tech University; Texas Tech University Health Sciences Center
Abstract
Cell cycle deregulation is strongly associated with the pathogenesis of prostate cancer. Clinical trials of cell cycle regulators that target either the G0/G1 or G2/M phase to inhibit the growth of cancers including prostate cancer are increasing. The present study focused on the cell cycle regulatory potential of the withanolide withaferin A (1) on prostate cancer cells. Compound 1 induced G2/M arrest in both prostate cancer cell lines (PC-3 and DU-145) when treated for 48 h. The G2/M arrest was accompanied by upregulation of phosphorylated Wee-1, phosphorylated histone H3, p21, and Aurora B. On the other hand, downregulation of cyclins (A2, B1, and E2) and a reduction in phosphorylated Cdc2 (Tyr15) were observed in 1-treated prostate cancer cells. In addition, decreased levels of phosphorylated Chk1 (Ser345) and Chk2 (Thr68) were evident in prostate cancer cells on treatment with 1. These results suggest that activation of Cdc2 leads to arrest in the M phase, with abnormal duplication, and initiation of mitotic catastrophe that results in cell death. In conclusion, these results show clearly the potential of 1 as a regulator of the G2/M phase of the cell cycle and as a therapeutic agent for prostate cancer.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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