Phytochemical composition and anticancer effects of Ardisia gigantifolia butanol extract subfractions: role of cell cycle arrest and senescence in cancer cell growth inhibition

Abstract Background The development of anticancer drugs derived from medicinal plants has recently attracted increasing attention due to advantages such as abundant natural resources and reduced side effects for patients.The present study aimed to explore the phytochemical composition and anticancer potential of butanol extract and its subfractions derived from Ardisia gigantifolia leaves. Methods and results Using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QToF-MS) analysis, 103 compounds were identified in the crude butanol extract, while 33–35 compounds were detected in each subfraction. MTT assay results showed that subfraction 5b (SubF5b) exhibited the strongest antiproliferative activity against MCF-7, MKN45, and AGS cancer cell lines, with IC 50 values ranging from 58.2 to 73.2 µg/mL, significantly lower than those of the crude extract and other subfractions, while showing low cytotoxicity toward normal breast epithelial MCF-10A cells. SubF5b induced G0/G1 phase arrest and pronounced cellular senescence, as evidenced by β-galactosidase staining. Molecular analyses showed significant downregulation of CDK4, CDK6, and CDK8, together with upregulation of the senescence markers P21 and P16 ( p < 0.01). Notably, P21 expression increased sevenfold at the mRNA level and 12-fold at the protein level. Proliferation markers Ki67 and PCNA were also significantly reduced ( p < 0.001), highlighting the potential of SubF5b as a multi-targeted anticancer agent. Conclusions This study highlights the anticancer potential of Ardisia gigantifolia , particularly SubF5b, which exhibits strong antiproliferative and senescence-inducing effects in cancer cells. These findings support its potential as a promising candidate for the development of plant-based therapeutics targeting tumor growth and progression.