Synergetic effects of aqueous extracts of Fuzi(Radix Aconiti Lateralis Preparata) and Tubeimu(Rhizoma Bolbostemmatis) on MDA-MB-231 and SKBR3 cells

OBJECTIVE: To test the synergistic effects of the aqueous extract of Tubeimu(Rhizoma Bolbostemmatis) and Fuzi(Radix Aconiti Lateralis Preparata) on MDA-MB-231 and SKBR3 breast cancer cells.METHODS: A combined index was created for the effects of Tubeimu(Rhizoma Bolbostemmatis) and Fuzi(Radix Aconiti Lateralis Preparata) extracts. Cell proliferation was performed by trypan blue exclusion and 3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assays. Flow cytometry was used to assess cell cycle distribution and apoptosis. Cell migration was determined by wound-healing and transwell assays. Confocal microscopy was used to detect E-cadherin and actin filaments.RESULTS: The aqueous extract from Tubeimu(Rhizoma Bolbostemmatis) and Fuzi(Radix Aconiti Lateralis Preparata) exerted synergetic effects on the growth of MDA-MB-231 cells and G1 phase arrest.When exposed to extracts at concentrations of 62.5∶62.5 and 62.5∶31.3 μg/m L, the combination index was 0.83 and 0.74, respectively. Interestingly, 62.5∶31.3 μg/m L of combined drugs enhanced the inhibitory effect of Tubeimu(Rhizoma Bolbostemmatis)on the migration of SKBR3 cells and reduced the stimulative effect of Fuzi(Radix Aconiti Lateralis Preparata)(P < 0.01), in which cells showed an increased expression of E-cadherin and reorganization of actin filaments(P < 0.001). 62.5∶62.5 μg/m L extract also synergistically induced apoptosis of MDA-MB-231 cells(P < 0.05 and P < 0.001). Acting as the main active ingredients in the extract, tubeimoside I and acetylbenzoylaconine at 10∶10 μg/m L and 5∶2.5 μg/m L also produced inhibitory effects on the proliferation and migration of cells(P <0.01).CONCLUSION: Tubeimu(Rhizoma Bolbostemmatis)and Fuzi(Radix Aconiti Lateralis Preparata) extracts had synergic effects on MDA-MB-231 and SKBR3 cells.