Mahanine synergistically enhances cytotoxicity of 5-fluorouracil through ROS-mediated activation of PTEN and p53/p73 in colon carcinoma (Retracted Article)
Mahanine synergistically enhances cytotoxicity of 5-fluorouracil through ROS-mediated activation of PTEN and p53/p73 in colon carcinoma (Retracted Article)
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DOI：
10.1007/s10495-013-0907-6
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发表时间：
2014-01-01
期刊：
影响因子：
7.2
通讯作者：
Mandal, Chitra
中科院分区：
文献类型：
--
作者：
Das, Ranjita;Bhattacharya, Kaushik;Mandal, Chitra
5-氟尿嘧啶（5-FU）单用或联用其他药物是结直肠癌化疗的主要基础，但微卫星不稳定患者普遍对5-FU治疗有耐药性。目前的研究主要集中在纯草药咔唑生物碱，mahanine，作为单独或与5-FU联合治疗结肠癌的机制。我们证明了mahanine诱导的细胞凋亡涉及活性氧（ROS）介导的PTEN核积累及其与p53/p73的相互作用。Mahanine和5-FU联合使用对细胞活力有协同抑制作用。这种组合也增强了ROS的产生，增加了肿瘤抑制蛋白并抑制了化学迁移。综上所述，我们的研究结果表明，马卡因可能是一种潜在的化疗药物，可以有效降低结肠癌中毒性5-FU的浓度。
5-Fluorouracil (5-FU) alone or in combination with other drugs is the main basis of chemotherapeutic treatment in colorectal cancer although patients with microsatellite instability generally show resistance to 5-FU treatment. The present investigation is focussed on the mechanistic insight of a pure herbal carbazole alkaloid, mahanine, as a single or in combination with 5-FU in colon cancer. We demonstrated that mahanine-induced apoptosis involved reactive oxygen species (ROS)-mediated nuclear accumulation of PTEN and its interaction with p53/p73. Mahanine and 5-FU in combination exerted synergistic inhibitory effect on cell viability. This combination also enhanced ROS production, increased tumour suppressor proteins and suppressed chemo-migration. Taken together, our results revealed that mahanine can be a potential chemotherapeutic agent with efficacy to reduce the concentration of toxic 5-FU in colon cancer.