Breast cancer is one of the most common causes of mortality in women. Lupiwighteone has anticancer effects in prostate cancer cells and neuroblastoma cells. However, the molecular and cellular mechanisms of lupiwighteone effects on human breast cancer cells are not as well known. In the present study, we investigated the effects of lupiwighteone on the proliferation and apoptosis of two different human cancer cells; MCF-7, an estrogen receptor (ER)-positive human breast cancer cell, and MDA-MB-231, a triple negative human breast cancer cell. Lupiwighteone treatment decreased the viability of MCF-7 and MDA-MB-231 cells. Lupiwighteone treatment resulted in apoptotic cell death in breast cancer cells, which was characterized by DNA fragmentation, accumulation of apoptotic cells, and nuclear condensation. We also showed that treatment with lupiwighteone induced caspase-dependent apoptosis (up-regulation of caspase-3, -7, -8, -9, PARP, and Bax or down-regulation of Bid, Bcl-2), induction of caspase-independent apoptosis (up-regulation of AIF and Endo G on cytosol), and inhibition of the PI3K/Akt/mTOR signaling pathway (down-regulation of PI3K, p-Akt, and p-mTOR) in both MCF-7 and MDA-MB-231 cells. These results suggest that lupiwighteone induces caspase-dependent and -independent apoptosis in both breast cancer cell lines via inhibiting PI3K/Akt/mTOR pathway.

中文翻译：

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Lupiwighteone通过抑制PI3K / Akt / mTOR途径诱导人乳腺癌细胞中caspase依赖性和非依赖性凋亡。

乳腺癌是女性死亡的最常见原因之一。Lupiwighteone对前列腺癌细胞和神经母细胞瘤细胞具有抗癌作用。然而，卢皮维特酮对人乳腺癌细胞的作用的分子和细胞机制尚不为人所知。在本研究中，我们研究了卢比维酮对两种不同人类癌细胞的增殖和凋亡的影响。雌激素受体（ER）阳性的人类乳腺癌细胞MCF-7和三阴性人类乳腺癌细胞MDA-MB-231。Lupiwighteone治疗会降低MCF-7和MDA-MB-231细胞的活力。Lupiwighteone治疗导致乳腺癌细胞凋亡，其特征是DNA片段化，凋亡细胞蓄积和核浓缩。我们还显示，用卢皮维特酮治疗可诱导caspase依赖性凋亡（caspase-3，-7，-8，-9，PARP和Bax上调或Bid，Bcl-2下调），caspase-诱导在MCF-7和MDA-M2中，独立的细胞凋亡（细胞溶质上的AIF和Endo G上调），以及PI3K / Akt / mTOR信号通路的抑制（PI3K，p-Akt和p-mTOR的下调） MB-231细胞。这些结果表明，lupiwighteone通过抑制PI3K / Akt / mTOR途径在两种乳腺癌细胞系中诱导caspase依赖性和非依赖性凋亡。p-Akt和p-mTOR）同时存在于MCF-7和MDA-MB-231细胞中。这些结果表明，lupiwighteone通过抑制PI3K / Akt / mTOR途径在两种乳腺癌细胞系中诱导caspase依赖性和非依赖性凋亡。p-Akt和p-mTOR）同时存在于MCF-7和MDA-MB-231细胞中。这些结果表明，lupiwighteone通过抑制PI3K / Akt / mTOR途径在两种乳腺癌细胞系中诱导caspase依赖性和非依赖性凋亡。