Recently,
traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-
tumor efficacy.
Celastrol and
Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as
Lei Gong Teng or Thunder of God Vine), have shown anti-
tumor effects.
Celastrol was identified as a natural 26 s
proteasome inhibitor which promotes cell apoptosis and inhibits
tumor growth. The effect and mechanism of
Triptolide on
prostate cancer (PCa) is not well studied. Here we demonstrated that
Triptolide, more potent than
Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines.
Triptolide also significantly inhibited the xenografted PC-3
tumor growth in nude mice. Moreover,
Triptolide induced PCa cell apoptosis through
caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific
protease 1 (SENP1) was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that
Triptolide down-regulated SENP1 expression in both
mRNA and
protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile,
Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the
Triptolide anti-PCa effects. Taken together, our data suggest that
Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-
tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa.