Tags

Type your tag names separated by a space and hit enter

Guggulsterone-induced apoptosis in human prostate cancer cells is caused by reactive oxygen intermediate dependent activation of c-Jun NH2-terminal kinase.
Cancer Res. 2007 Aug 01; 67(15):7439-49.CR

Abstract

Guggulsterone, a constituent of Indian Ayurvedic medicinal plant Commiphora mukul, causes apoptosis in cancer cells but the sequence of events leading to cell death is poorly understood. We now show that guggulsterone-induced cell death in human prostate cancer cells is caused by reactive oxygen intermediate (ROI)-dependent activation of c-Jun NH(2)-terminal kinase (JNK). Exposure of PC-3 and LNCaP cells to apoptosis inducing concentrations of guggulsterone resulted in activation of JNK and p38 mitogen-activated protein kinase (p38 MAPK) in both cell lines and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in LNCaP cells. The guggulsterone-induced apoptosis in PC-3/LNCaP cells was partially but statistically significantly attenuated by pharmacologic inhibition (SP600125) as well as genetic suppression of JNK activation. On the other hand, pharmacologic inhibition of p38 MAPK activation in PC-3 or LNCaP cells (SB202190) and ERK1/2 activation in LNCaP cells (PD98059) did not protect against guggulsterone-induced cell death. The guggulsterone treatment caused generation of ROI in prostate cancer cells but not in a normal prostate epithelial cell line (PrEC), which was also resistant to guggulsterone-mediated JNK activation. The guggulsterone-induced JNK activation as well as cell death in prostate cancer cells was significantly attenuated by overexpression of catalase and superoxide dismutase. In addition, guggulsterone treatment resulted in a decrease in protein level and promoter activity of androgen receptor in LNCaP cells. In conclusion, the present study reveals that the guggulsterone-induced cell death in human prostate cancer cells is regulated by ROI-dependent activation of JNK and guggulsterone inhibits promoter activity of androgen receptor.

Authors+Show Affiliations

Department of Pharmacology and Urology and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. singhs@upmc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17671214

Citation

Singh, Shivendra V., et al. "Guggulsterone-induced Apoptosis in Human Prostate Cancer Cells Is Caused By Reactive Oxygen Intermediate Dependent Activation of c-Jun NH2-terminal Kinase." Cancer Research, vol. 67, no. 15, 2007, pp. 7439-49.
Singh SV, Choi S, Zeng Y, et al. Guggulsterone-induced apoptosis in human prostate cancer cells is caused by reactive oxygen intermediate dependent activation of c-Jun NH2-terminal kinase. Cancer Res. 2007;67(15):7439-49.
Singh, S. V., Choi, S., Zeng, Y., Hahm, E. R., & Xiao, D. (2007). Guggulsterone-induced apoptosis in human prostate cancer cells is caused by reactive oxygen intermediate dependent activation of c-Jun NH2-terminal kinase. Cancer Research, 67(15), 7439-49.
Singh SV, et al. Guggulsterone-induced Apoptosis in Human Prostate Cancer Cells Is Caused By Reactive Oxygen Intermediate Dependent Activation of c-Jun NH2-terminal Kinase. Cancer Res. 2007 Aug 1;67(15):7439-49. PubMed PMID: 17671214.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Guggulsterone-induced apoptosis in human prostate cancer cells is caused by reactive oxygen intermediate dependent activation of c-Jun NH2-terminal kinase. AU - Singh,Shivendra V, AU - Choi,Sunga, AU - Zeng,Yan, AU - Hahm,Eun-Ryeong, AU - Xiao,Dong, PY - 2007/8/3/pubmed PY - 2007/9/12/medline PY - 2007/8/3/entrez SP - 7439 EP - 49 JF - Cancer research JO - Cancer Res. VL - 67 IS - 15 N2 - Guggulsterone, a constituent of Indian Ayurvedic medicinal plant Commiphora mukul, causes apoptosis in cancer cells but the sequence of events leading to cell death is poorly understood. We now show that guggulsterone-induced cell death in human prostate cancer cells is caused by reactive oxygen intermediate (ROI)-dependent activation of c-Jun NH(2)-terminal kinase (JNK). Exposure of PC-3 and LNCaP cells to apoptosis inducing concentrations of guggulsterone resulted in activation of JNK and p38 mitogen-activated protein kinase (p38 MAPK) in both cell lines and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in LNCaP cells. The guggulsterone-induced apoptosis in PC-3/LNCaP cells was partially but statistically significantly attenuated by pharmacologic inhibition (SP600125) as well as genetic suppression of JNK activation. On the other hand, pharmacologic inhibition of p38 MAPK activation in PC-3 or LNCaP cells (SB202190) and ERK1/2 activation in LNCaP cells (PD98059) did not protect against guggulsterone-induced cell death. The guggulsterone treatment caused generation of ROI in prostate cancer cells but not in a normal prostate epithelial cell line (PrEC), which was also resistant to guggulsterone-mediated JNK activation. The guggulsterone-induced JNK activation as well as cell death in prostate cancer cells was significantly attenuated by overexpression of catalase and superoxide dismutase. In addition, guggulsterone treatment resulted in a decrease in protein level and promoter activity of androgen receptor in LNCaP cells. In conclusion, the present study reveals that the guggulsterone-induced cell death in human prostate cancer cells is regulated by ROI-dependent activation of JNK and guggulsterone inhibits promoter activity of androgen receptor. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/17671214/Guggulsterone_induced_apoptosis_in_human_prostate_cancer_cells_is_caused_by_reactive_oxygen_intermediate_dependent_activation_of_c_Jun_NH2_terminal_kinase_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17671214 DB - PRIME DP - Unbound Medicine ER -