AIM Trichosantheskirilowii tuber extract (TKE) is traditional medicine used in East of Asia for patients with diabetes symptoms.TKE has been shown to have antitumor effects via G2/M cell cycle arrest, but the precise molecular mechanism by which it inhibits the proliferation of breast cancer cells remains unclear.Here, we study the efficacy of TKE as an anticancer agent in MCF-7 and MDA-MB-231 cells.METHODS Viability, cell cycle profiles, and mitochondrial membrane potential were measured by MTT assay and flow cytometry methods.Caspase activation and cell survival related molecular level were measured by western blot analysis and TUNEL assay.RESULTS TKE treatment of breast cancer cells resulted in significantly decreased cell growth and induced G2/M cell cycle arrest.G2/M cell cycle arrest of breast cancer cells was accompanied by increased poly(ADP-ribose) polymerase and caspase cleavage via mitochondria cytochrome C release.Further studies revealed that TKE treatment inhibited phospho-AKT expression in a time-dependent manner.CONCLUSION The results show that TKE modulates signal transduction pathways for inhibition of breast cancer cell growth and can be used as a anti-tumor agent.