Bitter melon extract inhibits breast cancer growth in preclinical model by inducing autophagic cell death.
Bitter melon extract inhibits breast cancer growth in preclinical model by inducing autophagic cell death.
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DOI：
10.18632/oncotarget.19887
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发表时间：
2017-09-12
期刊：
影响因子：
--
通讯作者：
Ray RB
中科院分区：
文献类型：
--
作者：
Muhammad N;Steele R;Isbell TS;Philips N;Ray RB
乳腺癌是全世界妇女的一个主要公共卫生问题，目前的治疗策略对这一致命疾病还不够有效。我们之前已经证明了苦瓜提取物（BME）在乳腺癌细胞中的抗增殖活性。在本研究中，我们观察到BME在乳腺癌细胞中诱导自噬体结合的长链3 (LC3)-B并积累p62/SQSTM1 （p62）蛋白。此外，我们观察到BME治疗乳腺癌细胞可增加phospho-AMPK表达并抑制mTOR/Akt信号通路。随后，我们证明BME喂养有效地抑制了同基因和异种移植小鼠模型的乳腺癌生长。此外，我们观察到bme喂养动物的肿瘤中p62积累增加，诱导自噬和凋亡细胞死亡。综上所述，我们的研究结果表明，BME治疗可以抑制乳腺癌肿瘤的生长，这种抗肿瘤活性在一定程度上是通过诱导自噬和调节AMPK/mTOR途径介导的。口服BME对乳腺癌模型的抗肿瘤活性表明其具有很高的临床应用潜力。
Breast cancer is a major public health problem worldwide in women and current therapeutic strategies are not adequately effective for this deadly disease. We have previously shown the anti-proliferative activity of bitter melon extract (BME) in breast cancer cells. In this study, we observed that BME treatment induces autophagosome-bound Long chain 3 (LC3)-B and accumulates protein p62/SQSTM1 (p62) in breast cancer cells. Additionally, we observed that BME treatment in breast cancer cells increases phospho-AMPK expression and inhibits the mTOR/Akt signaling pathway. Subsequently, we demonstrated that BME feeding effectively inhibited breast cancer growth in syngeneic and xenograft mouse models. Further, we observed the increased p62 accumulation, induction of autophagy and apoptotic cell death in tumors from BME-fed animals. Taken together, our results demonstrate that BME treatment inhibits breast tumor growth, and this anti-tumor activity in breast cancer is, in part, mediated by induction of autophagy and modulation of the AMPK/mTOR pathway. The antitumor activity of BME by oral feeding in breast cancer models suggested the high potential for a clinical application.
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