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

Abstract

ObjectiveTo 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. MethodsA 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. ResultsThe 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/mL, the combination index was 0.83 and 0.74, respectively. Interestingly, 62.5: 31.3 µg/mL 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/mL 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/mL and 5: 2.5 µg/mL also produced inhibitory effects on the proliferation and migration of cells (P < 0.01). ConclusionTubeimu (Rhizoma Bolbostemmatis) and Fuzi (Radix Aconiti Lateralis Preparata) extracts had synergic effects on MDA-MB-231 and SKBR3 cells.