Reactive oxygen species-dependent apoptosis by gugulipid extract of Ayurvedic medicine plant Commiphora mukul in human prostate cancer cells is regulated by c-Jun N-terminal kinase
Language: 
English
Abstract: 

Gugulipid (GL), extract of Indian Ayurvedic medicinal plant Commiphora mukul, has been used to treat a variety of ailments. We report an anticancer effect and mechanism of GL against human prostate cancer cells. Treatment with GL significantly inhibited the viability of human prostate cancer cell line LNCaP (androgen-dependent) and its androgen-independent variant (C81) with an IC(50) of ∼1 μM (24-h treatment), at pharmacologically relevant concentrations standardized to its major active constituent z-guggulsterone. The GL-induced growth inhibition correlated with apoptosis induction as evidenced by an increase in cytoplasmic histone-associated DNA fragmentation and sub-G(0)/G(1)-DNA fraction, and cleavage of poly(ADP-ribose) polymerase. The GL-induced apoptosis was associated with reactive oxygen species (ROS) production and c-Jun NH(2)-terminal kinase (JNK) activation. The induction of proapoptotic Bcl-2 family proteins Bax and Bak and a decrease of antiapoptotic Bcl-2 protein Bcl-2 were observed in GL-treated cells. SV40 immortalized mouse embryonic fibroblasts derived from Bax-Bak double-knockout mice were significantly more resistant to GL-induced cell killing compared with wild-type cells. It is interesting to note that a representative normal prostate epithelial cell line (PrEC) was relatively more resistant to GL-mediated cellular responses compared with prostate cancer cells. The GL treatment caused the activation of JNK that functioned upstream of Bax activation in apoptosis response. The GL-induced conformational change of Bax and apoptosis were significantly suppressed by genetic suppression of JNK activation. In conclusion, the present study indicates that ROS-dependent apoptosis by GL is regulated by JNK signaling axis.

Author(s): 
Xiao, Dong
Zeng, Yan
Prakash, Lakshmi
Badmaev, Vladmir
Majeed, Muhammed
Singh, Shivendra V.
Item Type: 
Journal Article
Publication Title: 
Molecular Pharmacology
Journal Abbreviation: 
Mol. Pharmacol.
Publication Date: 
Mar 2011
Publication Year: 
2011
Pages: 
499-507
Volume: 
79
Issue: 
3
ISSN: 
1521-0111
DOI: 
10.1124/mol.110.068551
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 21115635 PMCID: PMC3061364

Turabian/Chicago Citation

Dong Xiao, Yan Zeng, Lakshmi Prakash, Vladmir Badmaev, Muhammed Majeed and Shivendra V. Singh. Mar 2011. "Reactive oxygen species-dependent apoptosis by gugulipid extract of Ayurvedic medicine plant Commiphora mukul in human prostate cancer cells is regulated by c-Jun N-terminal kinase." Molecular Pharmacology 79: 3: 499-507. 10.1124/mol.110.068551.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1124/mol.110.068551 | issn = 1521-0111 | volume = 79 | pages = 499-507 | last = Xiao | first = Dong | coauthors = Zeng, Yan, Prakash, Lakshmi, Badmaev, Vladmir, Majeed, Muhammed, Singh, Shivendra V. | title = Reactive oxygen species-dependent apoptosis by gugulipid extract of Ayurvedic medicine plant Commiphora mukul in human prostate cancer cells is regulated by c-Jun N-terminal kinase | journal = Molecular Pharmacology | date = Mar 2011 | pmid = | pmc = }} </ref>