ArticleThe Journal of biological chemistry2009
ROCK mediates phorbol ester-induced apoptosis in prostate cancer cells via p21Cip1 up-regulation and JNK.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Induction of apoptosis and growth inhibition by silodosin and abiraterone acetate in PC-3 human prostate cancer cells.Investigative and clinical urology · 2025Article
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- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Article
- A Reverse-Osmosis Model of Apoptotic Shrinkage.Frontiers in cell and developmental biology · 2020Article
- Overlapping and unique roles played by ROCK1 and 2 in the modulation of coding and long noncoding RNA expression.BMC genomics · 2019Article
- Bacterial Toxins and Targeted Brain Therapy: New Insights from Cytotoxic Necrotizing Factor 1 (CNF1).International journal of molecular sciences · 2018Review
- The C1 domain of Vav3, a novel potential therapeutic target.Cellular signalling · 2017Article
- KLF5 promotes apoptosis induced by phorbol ester as an effector of the autocrine factor TNFα in LNCaP prostate cancer cells.Oncology letters · 2017Article
- Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1.Translational oncology · 2017Article
- 5‑bromo‑3‑(3‑hydroxyprop‑1‑ynyl)‑2H‑pyran‑2‑one induces apoptosis in T24 human bladder cancer cells through mitochondria-dependent signaling pathways.Molecular medicine reports · 2017Article
- Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by Modulating Multiple Cell Cycle Regulators.BioMed research international · 2017Article
- The lauric acid-activated signaling prompts apoptosis in cancer cells.Cell death discovery · 2017Article
- Review
- Coxsackie and adenovirus receptor is a critical regulator for the survival and growth of oral squamous carcinoma cells.Oncogene · 2014Article
- Article
- FERM domain of moesin desorbs the basic-rich cytoplasmic domain of l-selectin from the anionic membrane surface.Journal of molecular biology · 2013Article
- Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1.Molecular pharmacology · 2013Article
- Regulation of Transcriptional Networks by PKC Isozymes: Identification of c-Rel as a Key Transcription Factor for PKC-Regulated Genes.PloS one · 2013Article
- RhoA as a mediator of clinically relevant androgen action in prostate cancer cells.Molecular endocrinology (Baltimore, Md.) · 2012Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
It is established that androgen-dependent prostate cancer cells undergo apoptosis upon treatment with phorbol esters and related analogs, an effect primarily mediated by PKCdelta. Treatment of LNCaP prostate cancer cells with phorbol 12-myristate 13-acetate (PMA) causes a strong and sustained activation of RhoA and its downstream effector ROCK (Rho kinase) as well as the formation of stress fibers. These effects are impaired in cells subjected to PKCdelta RNA interference depletion. Functional studies revealed that expression of a dominant negative RhoA mutant or treatment with the ROCK inhibitor Y-27632 inhibits the apoptotic effect of PMA in LNCaP cells. Remarkably, the cytoskeleton inhibitors cytochalasin B and blebbistatin blocked not only PMA-induced apoptosis but also the activation of JNK, a mediator of the cell death effect by the phorbol ester. In addition, we found that up-regulation of the cell cycle inhibitor p21(Cip1) is required for PMA-induced apoptosis and that inhibitors of ROCK or the cytoskeleton organization prevent p21(Cip1) induction. Real time PCR analysis and reporter gene assay revealed that PMA induces p21(Cip1) transcriptionally in a ROCK- and cytoskeleton-dependent manner. p21(Cip1) promoter analysis revealed that PMA induction is dependent on Sp1 elements in the p21(Cip1) promoter but independent of p53. Taken together, our studies implicate ROCK-mediated up-regulation of p21(Cip1) and the cytoskeleton in PKCdelta-dependent apoptosis in prostate cancer cells.
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