Abstract
Pristimerin (PM), a quinonemethide triterpenoid, is a promising anticancer agent with potent antiproliferative and apoptosis-inducing activities against cancer cell lines. However, the anticancer activity and mechanisms of PM in prostate cancer cells have not been adequately investigated. Here we report that the degradation of survivin plays an important role in the antiproliferative and proapoptotic effects of PM in carcinoma of the prostate (CaP) cell lines. Treatment with PM inhibited proliferation and induced apoptosis in LNCaP and PC-3 cells as characterized by the loss of cell viability and an increase in Annexin V-binding and cleavage of PARP-1, respectively. The antiproliferative and apoptosis-inducing effects of PM were associated with the inhibition of cell cycle regulatory proteins, antiapoptotic survivin and members of the Bcl-2 family. Data showed that response to PM is regulated by survivin since overexpression of survivin rendered CaP cells resistant to PM. Furthermore, downregulation of survivin by PM was mediated through the ubiquitin-proteasomal degradation. Together, these data demonstrate that pristimerin inhibits proliferation and induces apoptosis in CaP cells by abolishing survivin through the ubiquitin-proteasome pathway.
Highlights
Herbal remedies are commonly used in traditional medicine to treat and prevent human diseases including cancer
We demonstrate that induction of apoptosis in carcinoma of the prostate (CaP) cells by PM is associated with inhibition of cell cycle regulatory proteins and proteasomal degradation of antiapoptotic survivin, a member of the inhibitors of apoptosis (IAP) family
Since cell division is regulated by cyclins and cyclin-dependent kinases and cdk inhibitors such as WAF1/21 and KIP1/27, we investigated the effect of PM on these cell cycle regulators
Summary
Herbal remedies are commonly used in traditional medicine to treat and prevent human diseases including cancer. PM inhibits proteasome activity, tumor cell migration and angiogenesis [8,14,15]
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