Improved chemosensitivity in cervical cancer to cisplatin: Synergistic activity of mahanine through STAT3 inhibition

被引：52
作者：
Das, Ranjita [1 ]
Bhattacharya, Kaushik [1 ]
Samanta, Suman K. [1 ]
Pal, Bikas C. [2 ]
Mandal, Chitra [1 ]
机构：
[1] CSIR Indian Inst Chem Biol, Canc Biol & Inflammatory Disorders Div, Kolkata 700032, India
[2] Natl Inst Pharmaceut Educ & Res, Kolkata, India
来源：
CANCER LETTERS | 2014年 / 351卷 / 01期
关键词：
Mahanine; Cisplatin; Cervical cancer; Synergism; STAT3; SIGNAL TRANSDUCER; LEUKEMIC-CELLS; APOPTOSIS; ACTIVATION; RESISTANCE; EXPRESSION; PATHWAY; TRANSCRIPTION-3; COMBINATION; CARCINOMA;
D O I：
10.1016/j.canlet.2014.05.005
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Toxicity reduction of cisplatin is necessary for improved treatment of cancer. Here we have demonstrated the synergistic growth-inhibitory effect of cisplatin on cervical cancer cells in-combination with a nontoxic herbal carbazole alkaloid, mahanine. Mahanine enhanced cisplatin-induced apoptosis and reduced its effective concentration similar to 5-8 folds. Mahanine inhibited JAK1 and Src and subsequently promoted proteasome-mediated degradation of STAT3. This event was further enhanced in-combination with cisplatin and subsequently inhibited cancer cell migration. Collectively, our results revealed that mahanine may be a prospective agent to reduce the concentration of cisplatin in adjunct for the treatment of cancer and thereby decreasing its toxicity. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：81 / 90
页数：10
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