Cryptotanshinone sensitizes DU145 prostate cancer cells to Fas(APO1/CD95)-mediated apoptosis through Bcl-2 and MAPK regulation.

Abstract:

:Fas/APO-1/CD95, a member of the tumor necrosis factor (TNF) receptor superfamily, is a potential anti-cancer factor as it can induce apoptosis in tumor cells. However, despite the fact that many cancer cells express Fas on the membrane, some tumors such as prostate cancer display resistance to Fas-induced apoptosis. In these cases, combination therapy using chemotherapeutic agents and Fas may be more suitable than therapy using Fas alone. In the present study, we demonstrate that the apoptosis inhibitory protein, Bcl-2, was highly expressed in response to Fas in DU145 prostate cancer cells, thereby conferring resistance to apoptosis. We have screened a number of naturally occurring products that may overcome this resistance. Here we report that cryptotanshinone, the major tanshinone isolated from Salvia miltiorrhiza Bunge, can suppress Bcl-2 expression and augment Fas sensitivity in DU145 cells. We further show that JNK and p38 MAPK act upstream of Bcl-2 expression in Fas-treated DU145 cells, and that cryptotanshinone significantly blocked activation of these kinases. Moreover, cryptotanshinone sensitized several tumor cells to a broad range of anti-cancer agents. Collectively, our data suggest that cryptotanshinone has therapeutic potential in the treatment of human prostate cancer.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Park IJ,Kim MJ,Park OJ,Park MG,Choe W,Kang I,Kim SS,Ha J

doi

10.1016/j.canlet.2010.06.006

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

88-98

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(10)00318-6

journal_volume

298

pub_type

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