Limocitrin Suppresses Breast Cancer Through Inducing Apoptotic-Cell Death Signaling and Inhibiting the PI3K/AKT/mTOR/S6K Cell Survival Signaling

The discovery of limocitrin in Sedum sarmentosum Bunge, a compound known for its potent antitumor activity, has sparked interest in understanding its molecular mechanisms and bioactive effects. Breast cancer, particularly triple-negative breast cancer (TNBC), presents a challenging prognosis with a higher likelihood of recurrence, metastasis, and lower survival rates compared to most other cancer types. This study aimed to explore the anticancer potential of limocitrin on two different human breast cancer cell lines. The results of the study revealed that limocitrin effectively reduced the viability of breast cancer cells, with IC50 values of 29.33 +/- 0.010 and 28.70 +/- 0.030 mu M for MDA-MB-231 and MCF-7 cells, respectively. Further investigations demonstrated that limocitrin induced apoptotic cell death, characterized by an increase in the population of apoptotic cells and the formation of apoptotic bodies. Limocitrin induced the upregulation of apoptosis-related protein expressions such as apoptosis-inducing factor, Bax, endonuclease G, and cleaved-poly ADP-ribose polymerase, while downregulating the expression of proteins associated with cell survival, including Akt, Bcl-2, Bid, mTOR, PI3K, procaspases, and p70 S6 kinase. Notably, the response to limocitrin treatment varied between the two types of breast cancer cells, indicating a differential effect of limocitrin on the intracellular signaling pathways related to cell survival in breast cancer. These findings open up avenues for further research and exploration of limocitrin as a potential therapeutic agent for breast cancer treatment, especially for challenging subtypes like TNBC.