Regulation of hippo signaling mediated apoptosis by Rauvolfia tetraphylla in triple-negative breast cancer.

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.

Network pharmacology integrated with molecular docking reveals the anticancer mechanism of Jasminum sambac Linn. essential oil against human breast cancer and experimental validation by in vitro and in vivo studies.

Jasminum sambac L. (J. sambac) belongs to the family Oleaceae and it is an ornamental subtropical evergreen shrub used in traditional treatments of certain ailments and diseases. This study aimed at devising an integrated strategy attempts to evaluate the bioactive components in the J. sambac essential oil (JEO) against human breast cancer. JEO extracted by distillation process and analyzed by GC-MS was subjected to screening of therapeutic components in their allegiance to the drug-likeness index. The utility and efficacy of its molecular mechanism relating to anticancer potential were probed with network pharmacology analysis. Gene ontology, pathway enrichment, and compound-target-pathway network by Cytoscape helped to harp on hub targets and pathways involved in curative action. Drawing from the network data, molecular docking analysis of selected compounds on breast cancer targets was approached. The anti-proliferative study was carried out in MCF-7 and MDA-MB-231 to evaluate the cytotoxicity of JEO. Finally, in vivo anticancer activity was verified using rat models. The results showed MDA-MB-231 cell growth was highly inhibited than the MCF-7 cell line. Alongside this in vitro trial, in situ effectiveness of JEO was evaluated using female Sprague-Dawley rat animal models. In vivo experiments and histopathological analysis showed convincing results in DMBA tumor-induced rats. The larger aim of this study is to identify the potential ingredients of the JEO in cancer apoptosis by integrating network pharmacology and experimental validation achieved to certain extent confers credence to the concept of hiring J. sambac as floral therapy in dealing with the disastrous disease.