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首页> 美国卫生研究院文献>other >The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways
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The Anti-Cancer Activities of Vernonia amygdalina Extract in Human Breast Cancer Cell Lines Are Mediated through Caspase-Dependent and p53-Independent Pathways

机译：杏仁核Vernonia提取物在人乳腺癌细胞系中的抗癌活性通过胱天蛋白酶依赖性和p53依赖性途径介导。

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Breast cancer is currently the leading cause of cancer-related deaths among women globally. Notably, medicinal plant extracts may be a potential source for treatments of breast cancer. Vernonia amygdalina (VA) is a woody shrub reported to have not only diverse therapeutic effects but also anti-cancer properties. However, current research about the mechanisms of the anti-cancer potential of VA has been limited. This study aimed to investigate the mechanisms of action of VA that underlie its anti-cancer effects in human breast cancer cell lines (MCF-7 and MDA-MB-231 cells). Results from MTT assay revealed that VA inhibits the proliferation of MCF-7 and MDA-MB-231, in a time- and dose-dependent manner. The underlying mechanism of this growth inhibition involved the stimulation of cell-type specific G1/S phase cell cycle arrest in only MCF-7 cells, and not in MDA-MB-231 cells. While the growth arrest was associated with increased levels of p53 and p21, and a concomitant decrease in the levels of cyclin D1 and cyclin E, it was shown that VA causes cell cycle arrest through a p53-independent pathway as tested by the wild type p53 inhibitor, pifithrin-α. Furthermore, this study revealed that VA induces apoptosis in the two cell lines, as indicated by the increase in Annexin V-positive cells and sub-G1 population, and that this VA-induced apoptosis occurred through both extrinsic and intrinsic apoptotic pathways. The apoptosis in MCF-7 cells was also likely to be caspase-dependent and not p53 transcriptional-dependent. Given that approximately 70% of diagnosed breast cancers express ER-α, a crucial finding was that VA inhibits the expression of ER-α and its downstream player, Akt, highlighting the potential clinical significance of VA. Moreover, VA exhibits synergism when combined with doxorubicin, suggesting that it can complement current chemotherapy. Overall, this study demonstrates the potential applications of VA as an anti-cancer drug for breast cancer treatment.
机译：当前，乳腺癌是全球女性与癌症相关的死亡的主要原因。值得注意的是，药用植物提取物可能是治疗乳腺癌的潜在来源。杏仁核藜（VA）是一种木质灌木，据报道不仅具有多种治疗效果，而且具有抗癌特性。但是，关于VA的抗癌潜力机理的当前研究是有限的。这项研究旨在研究VA在人乳腺癌细胞系（MCF-7和MDA-MB-231细胞）中的抗癌作用基础的作用机理。 MTT分析的结果表明，VA以时间和剂量依赖性方式抑制MCF-7和MDA-MB-231的增殖。这种生长抑制的潜在机制涉及仅在MCF-7细胞中而不在MDA-MB-231细胞中刺激细胞类型特异性G1 / S期细胞周期停滞。尽管生长停滞与p53和p21的水平升高以及细胞周期蛋白D1和细胞周期蛋白E的水平降低相关，但已证明VA通过野生型p53的检测通过非p53依赖性途径引起细胞周期停滞。抑制剂，菲菲菌素-α。此外，这项研究表明，如膜联蛋白V阳性细胞和亚G1群体的增加所表明，VA诱导了这两种细胞系的凋亡，并且这种VA诱导的凋亡通过外在和内在的凋亡途径发生。 MCF-7细胞中的凋亡也可能是caspase依赖性的，而不是p53转录依赖性的。鉴于大约70％的已诊断乳腺癌表达ER-α，一个关键的发现是VA抑制ER-α及其下游分子Akt的表达，从而突出了VA的潜在临床意义。此外，VA与阿霉素联用时表现出协同作用，表明它可以补充目前的化学疗法。总的来说，这项研究证明了VA作为抗癌药物在乳腺癌治疗中的潜在应用。

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