Reference - Detail
| RRC ID | 67209 |
|---|---|
| Author | Nishikawa Y, Okuzaki D, Fukushima K, Mukai S, Ohno S, Ozaki Y, Yabuta N, Nojima H. |
| Title | Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells. |
| Journal | PLoS One |
| Abstract |
Withaferin A (WA), a major bioactive component of the Indian herb Withania somnifera, induces cell death (apoptosis/necrosis) in multiple types of tumor cells, but the molecular mechanism underlying this cytotoxicity remains elusive. We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD). WA also killed PC-3 cells in spheroid-forming medium. DNA microarray analysis revealed that WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs) in PC-3 and DU-145, but not in LNCaP and TIG-1. Western analysis revealed increased expression of c-Fos and reduced expression of the anti-apoptotic protein c-FLIP(L). Expression of HSPs such as HSPA6 and Hsp70 was conspicuously elevated; however, because siRNA-mediated depletion of HSF-1, an HSP-inducing transcription factor, reduced PC-3 cell viability, it is likely that these heat-shock genes were involved in protecting against cell death. Moreover, WA induced generation of reactive oxygen species (ROS) in PC-3 and DU-145, but not in normal fibroblasts. Immunocytochemistry and immuno-electron microscopy revealed that WA disrupted the vimentin cytoskeleton, possibly inducing the ROS generation, c-Fos expression and c-FLIP(L) suppression. These observations suggest that multiple events followed by disruption of the vimentin cytoskeleton play pivotal roles in WA-mediated cell death. |
| Volume | 10(7) |
| Pages | e0134137 |
| Published | 2015-1-1 |
| DOI | 10.1371/journal.pone.0134137 |
| PII | PONE-D-15-06792 |
| PMID | 26230090 |
| PMC | PMC4521694 |
| MeSH | Androgens / metabolism* Autophagy Cell Death / drug effects* Cell Line, Tumor Culture Media, Serum-Free Drug Resistance, Neoplasm Endoplasmic Reticulum / drug effects Fibroblasts / cytology Fibroblasts / metabolism Gene Expression Regulation, Neoplastic Humans Male Mitochondria / drug effects Prostatic Neoplasms / metabolism Prostatic Neoplasms / pathology* Proto-Oncogene Proteins c-fos / metabolism Subcellular Fractions / metabolism Up-Regulation Vimentin / metabolism Withanolides / pharmacology* |
| IF | 2.74 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 10 |
| Altmetric score changes over past 6months | 0.2 |
| Resource | |
| Human and Animal Cells | PC-3(RCB2145) DU145(RCB2143) |