Osthole enhances doxorubicin-induced apoptosis in p53-wildtype prostate cancer cells by down-regulating SIRT1 expression / 中国病理生理杂志
Chinese Journal of Pathophysiology
;
(12): 435-440, 2018.
Article
in Chinese
| WPRIM
| ID: wpr-701140
ABSTRACT
AIM:
To investigate the effect and mechanism of osthole on increasing the cytotoxicity of doxorubi -cin(DOX)to prostate cancer cells.METHODS:
MTT assay was performed to evaluate the viability of LNCaP cells trea-ted with osthole and DOX.The protein expression of silent information regulator 1(SIRT1),p53,acetylated p53 and Pu-ma,as well as release of cytochrome C and activation of caspase-9 and caspase-3 in the LNCaP cells treated with osthole and DOX were determined by Western blot.The apoptosis of the LNCaP cells treated with osthole and DOX was analyzed by flow cytometry.RESULTS:
Osthole significantly increased the cytotoxicity of DOX against p 53-wildtype prostate cancer cell line LNCaP.Osthole significantly inhibited the expression of SIRT 1 in the LNCaP cells.Transfection with SIRT1 plas-mid decreased the cytotoxicity of osthole and DOX co-treatment against LNCaP cells.Combination with osthole and DOX significantly induced the over-expression and acetylation of p53.Transfection with p53 siRNA significantly decreased the synergistic effect of osthole on cytotoxicity of DOX-treated LNCaP cells.Combination with osthole and DOX significantly in-duced the release of cytochrome C into the cytoplasm from mitochondria,followed by activation of caspase-9 and its down-stream molecule caspase-3,thus leading to cell apoptosis in the LNCaP cells.CONCLUSION:
Osthole promotes the p53-dependent apoptosis in DOX-treated prostate cancer LNCaP cells by down-regulating the expression of SIRT1.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
Chinese Journal of Pathophysiology
Year:
2018
Type:
Article
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