Steroids from Commiphora mukul display antiproliferative effect against human prostate cancer PC3 cells via induction of apoptosis.
Two new stigmastane-type steroids, stigmasta-5,22E-diene-3β,11α-diol (1) and stigmasta-5,22E-diene-3β,7α,11α-triol (2), together with eight known compounds, were isolated from the resinous exudates of Commiphora mukul. Their structures were established by extensive analysis of their HR-MS, 1D- and 2D-NMR (COSY, HMQC, HMBC and NOESY) spectra. The isolates were evaluated for their antiproliferative activities against four human cancer cell lines. Compound 2 demonstrated inhibitory effects with IC(50) values of 5.21, 9.04, 10.94 and 16.56 μM, respectively, against K562, MCF-7, PC3 and DU145 human cancer cell lines. Further study showed that 2 was able to enforce the PC3 cell cycle arrest in the G2/M phase, and induce the apoptosis of PC3 cells by activation of Bax, caspases 3 and 9, and by inhibition of Bcl-2. It was also found that 1 inhibited proliferation of PC3 cells via G0/G1 phase arrest of the cell cycle.
School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan 250012, PR China.
Tao
T
Shen
Li
L
Zhang
Yan-Yan
YY
Wang
Pei-Hong
PH
Fan
Xiao-Ning
XN
Wang
Zhao-Min
ZM
Lin
Hong-Xiang
HX
Lou
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D029744:Commiphora / Q000737:chemistry*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000473:pathology*; D013256:Steroids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D013329:Structure-Activity Relationship
D013256:Steroids