Pterostilbene Suppresses Ovarian Cancer Growth via Induction of Apoptosis and Blockade of Cell Cycle Progression Involving Inhibition of the STAT3 Pathway

被引:52
作者
Wen, Wei [1 ]
Lowe, Gina [2 ]
Roberts, Cai M. [3 ]
Finlay, James [4 ]
Han, Ernest S. [1 ]
Glackin, Carlotta A. [2 ]
Dellinger, Thanh Hue [1 ]
机构
[1] City Hope Comprehens Canc Ctr, Dept Surg, Div Gynecol Oncol, 1500 E Duarte Rd,Machris 1128, Duarte, CA 91010 USA
[2] Beckman Res Inst, Dept Dev & Stem Cell Biol, Duarte, CA 91010 USA
[3] Yale Univ, Dept Obstet & Gynecol, Yale, CT 06520 USA
[4] Beckman Res Inst, Ctr Comparat Med, Duarte, CA 91010 USA
基金
美国国家卫生研究院;
关键词
pterostilbene; ovarian cancer; cisplatin; combination; synergy; TARGETED THERAPIES; RESVERATROL; BIOAVAILABILITY; EXPRESSION; ARREST; MODEL;
D O I
10.3390/ijms19071983
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A growing body of evidence has demonstrated the promising anti-tumor effects of resveratrol in ovarian cancer cells, including its inhibitory effects on STAT3 activation. Nonetheless, the low bioavailability of resveratrol has reduced its attractiveness as a potential anti-cancer treatment. In contrast, pterostilbene, a stilbenoid and resveratrol analog, has demonstrated superior bioavailability, while possessing significant antitumor activity in multiple solid tumors. In this study, the therapeutic potential of pterostilbene was evaluated in ovarian cancer cells. Pterostilbene reduces cell viability in several different ovarian cancer cell lines by suppressing cell cycle progression and inducing apoptosis. Further molecular study has shown that pterostilbene effectively suppressed phosphorylation of STAT3, as well as STAT3 downstream genes that regulate cell cycle and apoptosis, indicating that inhibition of STAT3 pathway may be involved in its anti-tumor activity. The addition of pterostilbene to the commonly used chemotherapy cisplatin demonstrated synergistic antiproliferative activity in several ovarian cancer cell lines. Pterostilbene additionally inhibited cell migration in multiple ovarian cancer cell lines. The above results suggest that pterostilbene facilitates significant anti-tumor activity in ovarian cancer via anti-proliferative and pro-apoptotic mechanisms, possibly via downregulation of JAK/STAT3 pathway. Pterostilbene thus presents as an attractive non-toxic alternative for potential adjuvant or maintenance chemotherapy in ovarian cancer.
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页数:12
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