Abstract

Background/Objectives: Breast cancer is the most commonly diagnosed cancer among women worldwide, with triple-negative breast cancer (TNBC) being a highly aggressive subtype characterized by early recurrence, limited targeted therapies, and poor clinical outcomes. Despite advances in chemotherapy, therapeutic resistance remains a major challenge, underscoring the need for alternative therapeutic approaches. Natural products continue to serve as important sources of bioactive compounds for cancer drug discovery. Tiliacora triandra, a Thai medicinal plant traditionally used to manage inflammatory and metabolic disorders, has not been extensively investigated for its potential against TNBC. In this study, we evaluated the anti-cancer effects of T. triandra extracts and its major flavonoid constituent, pectolinarigenin, in triple-negative breast cancer, MDA-MB-231 cells. Methods: An 80% ethanolic root extract was sequentially partitioned into hexane, dichloromethane, and ethyl acetate fractions. High-performance liquid chromatography identified pectolinarigenin as a predominant component of the dichloromethane fraction (TT-DCM), with a quantified content of 14.24 ± 2.32 mg/g extract. The anti-cancer effect of TT-DCM and pectolinarigenin on MDA-MB-231 cells were investigated using colony formation, cell cycle analysis, PI/Annexin V staining, and Western blot analysis. Results: Both TT-DCM and pectolinarigenin significantly reduced MDA-MB-231 cell viability and clonogenic growth. Treatment resulted in G0/G1 phase accumulation, accompanied by decreased expression of cyclin D1, CDK2, and CDK4. Apoptotic induction was observed, as evidenced by lower expression levels of Bcl-xL, Bcl-2, and surviving proteins, together with increased caspase-9 and caspase-3 activities. Additionally, TT-DCM and pectolinarigenin were associated with reduced phosphorylation of ERK1/2, JNK1/2, and p38 MAPKs. Conclusions: Collectively, these findings demonstrate that pectolinarigenin derived from T. triandra exerts potent anti-cancer activity in MDA-MB-231 TNBC cells through coordinated modulation of cell cycle progression, apoptotic signaling, and MAPK pathway activity. Further studies are warranted to validate these effects in additional TNBC models.