+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Phorbol ester-induced apoptosis in prostate cancer cells via autocrine activation of the extrinsic apoptotic cascade: a key role for protein kinase C delta



Phorbol ester-induced apoptosis in prostate cancer cells via autocrine activation of the extrinsic apoptotic cascade: a key role for protein kinase C delta



Journal of Biological Chemistry 280(47): 38982-38991



It is well established that activation of protein kinase C (PKC) by phorbol esters promotes apoptosis in androgen-dependent prostate cancer cells. However, there is limited information regarding the cellular mechanisms involved in this effect. In this report we identified a novel autocrine pro-apoptotic loop triggered by PKC[delta] activation in prostate cancer cells that is mediated by death receptor ligands. The apoptotic effect of phorbol 12-myristate 13-acetate in LNCaP cells was impaired by inhibition or depletion of tumor necrosis factor alpha-converting enzyme, the enzyme responsible for tumor necrosis factor [alpha] (TNF[alpha]) shedding. Moreover, the apoptogenic effect of conditioned medium collected after phorbol 12-myristate 13-acetate treatment could be inhibited by blocking antibodies against TNF[alpha] and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), but not FasL, as well as by RNA interference depletion of TNF[alpha] and TRAIL receptors. Moreover, depletion or inhibition of death receptor downstream effectors, including caspase-8, FADD, p38 MAPK, and JNK, significantly reduced the apoptogenic effect of the conditioned medium. PKC[delta] played a major role in this autocrine loop, both in the secretion of autocrine factors as well as a downstream effector. Taken together, our results demonstrate that activation of PKC[delta] in prostate cancer cells causes apoptosis via the release of death receptor ligands and the activation of the extrinsic apoptotic cascade.

(PDF emailed within 0-6 h: $19.90)

Accession: 012412137

Download citation: RISBibTeXText

PMID: 16183650

DOI: 10.1074/jbc.M506767200


Related references

Neutral endopeptidase promotes phorbol ester-induced apoptosis in prostate cancer cells by inhibiting neuropeptide-induced protein kinase C delta degradation. Cancer Research 60(23): 6590-6596, 2000

Involvement of protein kinase C delta (PKCdelta) in phorbol ester-induced apoptosis in LNCaP prostate cancer cells. Lack of proteolytic cleavage of PKCdelta. Journal of Biological Chemistry 275(11): 7574-7582, 2000

Bryostatin 1 inhibits phorbol ester-induced apoptosis in prostate cancer cells by differentially modulating protein kinase C (PKC) delta translocation and preventing PKCdelta-mediated release of tumor necrosis factor-alpha. Molecular Pharmacology 78(3): 325-332, 2010

A protein kinase C/protein kinase D pathway protects LNCaP prostate cancer cells from phorbol ester-induced apoptosis by promoting ERK1/2 and NF-{kappa}B activities. Carcinogenesis 32(8): 1198-1206, 2011

Phorbol ester-induced apoptosis of human prostate cancer cells involves prolonged activation of the MAP kinase pathway and correlates with expression of RasGRP mRNA. Proceedings of the American Association for Cancer Research Annual Meeting 40: 580, March, 1999

Involvement of protein kinase C d (PKCd) in phorbol ester-induced apoptosis in LNCaP prostate cancer cells. Lack of proteolytic cleavage of PKCd. The Journal of Biological Chemistry 275(11): 74-82, 2000

A role for protein kinase C delta in the differential sensitivity of MCF-7 and MDA-MB 231 human breast cancer cells to phorbol ester-induced growth arrest and p21(WAFI/CIP1) induction. Cancer Letters 172(1): 43-53, 2001

Phorbol ester-induced apoptosis is accompanied by NGFI-A and c-fos activation in androgen-sensitive prostate cancer cells. Cell Growth & Differentiation 5(7): 735-741, 1994

Phorbol ester inhibits DNA damage-induced apoptosis in U937 cells through activation of protein kinase C. Life Sciences 65(21): 2251-2258, Oct 15, 1999

Regulation of Ras.GTP loading and Ras-Raf association in neonatal rat ventricular myocytes by G protein-coupled receptor agonists and phorbol ester. Activation of the extracellular signal-regulated kinase cascade by phorbol ester is mediated by Ras. Journal of Biological Chemistry 274(28): 19762-19770, 1999

Phorbol ester-induced cIAP2 expression in human colon cancer cells is dependent on the novel protein kinase C-delta. Proceedings of the American Association for Cancer Research Annual Meeting 43: 530, March, 2002

Mitochondrial translocation of protein kinase C delta in phorbol ester-induced cytochrome c release and apoptosis. Journal of Biological Chemistry 275(29): 21793-6, 2000