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Regulation of hippo signaling mediated apoptosis by Rauvolfia tetraphylla in triple-negative breast cancer
Medical Oncology ( IF 3.4 ) Pub Date : 2024-03-29 , DOI: 10.1007/s12032-024-02341-5
B. Balavaishnavi , M. Kamaraj , T. G. Nithya , P. Santhosh , S. GokilaLakshmi , Mohammed Rafi Shaik

Rauvolfia tetraphylla is an essential medicinal plant that has been widely used in traditional medicine for various disease treatments. However, the tumor suppressor activity of R. tetraphylla and its phytocompounds were not explored against triple-negative breast cancer. The current research investigated the impact of R. tetraphylla methanolic extract (RTE) and its isolated compounds Ajmaline (RTC1) and Reserpine (RTC2) on triple-negative breast cancer cell line (MDA-MB-231) focusing on anti-proliferative effects. Our study imparts that RTE and RTC2 showed promising cytotoxic effects compared to RTC1. So further experiments have proceeded with RTE and RTC2, to evaluate its proliferation, migration, and apoptotic effect. The result shows around 80% of cells were observed in the G0/G1 phase in cell cycle analysis indicating the cell cycle inhibition and duel staining clearly showed the apoptotic effect. The migration of cells after the scratch was 60.45% observed in control and 90% in treated cells showing the inhibition of migration. ROS distribution was intense compared to control indicating the increased ROS stress in treated cells. Both RTE and RTC2-treated cells showed the potential to suppress proliferation and induce apoptotic change by upregulating BAX and MST-1 and suppressing Bcl2, LATS-1, and YAP, proving that deregulation of YAP resulting in the blockage of TEAD-YAP complex and inhibit proliferation. Therefore, R. tetraphylla extract and its isolated compounds were demonstrated to find its ability to act against MDA-MB-231 and these findings will help adjudicate it as a therapeutic drug against experimental triple-negative breast cancer.



中文翻译:

三阴性乳腺癌中萝芙木对河马信号介导细胞凋亡的调节

萝芙木是一种重要的药用植物,在传统医学中广泛用于治疗各种疾病。然而,尚未研究四叶红及其植物化合物对三阴性乳腺癌的抑癌活性。目前的研究调查了四叶红甲醇提取物 (RTE) 及其分离化合物 Ajmaline (RTC1) 和利血平 (RTC2) 对三阴性乳腺癌细胞系 (MDA-MB-231) 的影响,重点关注抗增殖作用。我们的研究表明,与 RTC1 相比,RTE 和 RTC2 显示出有希望的细胞毒性作用。因此,我们对RTE和RTC2进行了进一步的实验,以评估其增殖、迁移和凋亡作用。结果显示,细胞周期分析中大约80%的细胞处于G0/G1期,表明细胞周期受到抑制,双重染色清楚地显示出凋亡效应。在对照组中观察到划痕后细胞的迁移率为 60.45%,在处理细胞中观察到的细胞迁移率为 90%,显示迁移受到抑制。与对照相比,ROS 分布强烈,表明处理细胞中 ROS 应激增加。 RTE 和 RTC2 处理的细胞均显示出通过上调 BAX 和 MST-1 以及抑制 Bcl2、LATS-1 和 YAP 来抑制增殖并诱导凋亡变化的潜力,证明 YAP 的失调导致 TEAD-YAP 复合物的阻断,并诱导细胞凋亡。抑制增殖。因此,R .四叶草提取物及其分离化合物已被证明具有对抗 MDA-MB-231 的能力,这些发现将有助于判定其作为实验性三阴性乳腺癌的治疗药物。

更新日期:2024-03-30
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