Abstract：
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.
摘要：
乌叶草是一种重要的药用植物，已广泛用于传统医学中的各种疾病治疗。然而,未对三阴性乳腺癌进行研究。目前的研究调查了R.tetraphlla甲醇提取物（RTE）及其分离的化合物Ajmaline（RTC1）和利血平（RTC2）对三阴性乳腺癌细胞系（MDA-MB-231）的影响，重点是抗增殖作用。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，对RTE和RTC2进行了进一步的实验，以评估其增殖，迁移,和凋亡效应。结果显示在细胞周期分析中在G0/G1期观察到约80%的细胞,表明细胞周期抑制和决斗染色清楚地显示凋亡作用。划痕后的细胞迁移在对照中观察到60.45%,在处理的细胞中观察到90%,显示出迁移的抑制。与对照相比,ROS分布强烈,表明在处理的细胞中增加的ROS应激。RTE和RTC2处理的细胞均显示出通过上调BAX和MST-1并抑制Bcl2，LATS-1和YAP来抑制增殖和诱导凋亡变化的潜力，证明YAP的失调导致TEAD-YAP复合物的阻断并抑制增殖。因此,证明了四叶草提取物及其分离的化合物具有抗MDA-MB-231的能力，这些发现将有助于裁定其作为实验性三阴性乳腺癌的治疗药物。
