The Potential of Eleutherine bulbosa in Inducing Apoptosis and Inhibiting Cell Cycle in Breast Cancer: A Network Pharmacology Approach and In Vitro Experiments.

OBJECTIVE: The objective of this study was to evaluate the potential and mechanisms of phytochemicals in Eleutherine bulbosa (EBE) in inducing apoptosis and inhibiting the cell cycle in breast cancer through a network pharmacology approach and in vitro validation. METHODS: This research employed a literature review approach to identify active anti-cancer compounds and utilized a network pharmacology approach to predict the mechanisms of action of EBE compounds in breast cancer. In addition, in vitro experiments were conducted using MTT method to evaluate the effects of EBE on the cytotoxicity of T47D cells, and the flow cytometry method was employed to determine the impact of EBE on apoptosis and the cell cycle. RESULTS: The network pharmacology analysis revealed that EBE had an impact on 42 genes involved in breast cancer, including 23 important target genes implicated in the pathophysiology of breast cancer. Pathway analysis using the KEGG database showed a close association between EBE and crucial signaling pathways in breast cancer, including P53 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, apoptosis and cell cycle. In vitro experiments demonstrated that EBE exhibited moderate anti-cancer activity. Furthermore, EBE demonstrated significant potential in inducing apoptosis in breast cancer cells, with a percentage of apoptotic cells reaching 93.6%. Additionally, EBE was observed to disrupt the cell cycle, leading to a significant increase in the sub G1 and S phases, and a significant decrease in the G2-M and G1 phases. CONCLUSION: EBE has the potential to be an anti-cancer agent through various mechanisms, including apoptosis induction and cell cycle inhibition in breast cancer cells. These findings provide new insights into the potential of EBE as an alternative treatment for breast cancer.

Association between GPER gene polymorphisms and GPER expression levels with cancer predisposition and progression.

Estrogen is a female sex steroid hormone that plays a significant role in physiological functions. Evidence suggests that estrogen-signaling pathways are closely linked to cancer development and progression. The novel G protein-coupled estrogen receptor (GPER or GPR30) has been shown to influence cancer predisposition and progression, although results of related studies remain equivocal. Thus, this meta-analysis aimed to estimate the relationship between GPER gene polymorphisms and GPER expression levels, with cancer predisposition and progression. The pooled results showed that two GPER polymorphisms, rs3808350 and rs3808351, were significantly associated with cancer predisposition, especially in the Asian population, but no significant association was detected for rs11544331. In parallel, we also found that cancer aggressiveness and progression correlated with rs3808351 and GPER expression in cancerous tissues. Altogether, our findings suggest that GPER plays a pivotal role in cancer pathogenesis and progression. We suggest that rs3808350 and rs3808351 may be used as a prospective biomarker for cancer screening; while rs3808351 and GPER expression can be used to examine the prognosis of patients with cancer. Further biological studies are warranted to confirm our findings.