Anemoside B4 sensitizes human colorectal cancer to fluorouracil-based chemotherapy through src-mediated cell apoptosis

Abstract

Currently, 5-Fluorouracil (5-FU) based chemotherapy is the primary option for colorectal cancer after surgery, whereas chemotherapy resistance related mortality is observed in a large proportion of patients. Anemoside B4 (AB4) is a triterpene saponin, which exhibits a considerable activity in oncotherapy. In this study, we explored the efficacy of AB4 in FU-based chemotherapy in colorectal cancer cells and the underlying molecular mechanisms. Our results indicated a significant synergistic activity of AB4 in 5-FU treated colorectal cancer cells. Furthermore, AB4 treatment eliminated colorectal cancer stem cells by promoting apoptotic cell death in 5-FU resistant colorectal cancer cells. Mechanically, AB4 activated caspase-9 pathway in 5-FU resistant colorectal cancer cells. Elevated Src activity induced cell apoptosis and cancer stem cells elimination effects in AB4 treated colorectal cancer cells. In conclusion, AB4 showed promising sensitization effect in the FU-based chemotherapy of colorectal cancer. Our study may pave a way to ameliorate FU-based chemotherapeutic efficiency in colorectal cancer.

Saponins as cytotoxic agents: an update (2010–2021). Part II—Triterpene saponins

“…It should be noted that a combination of 5-FU and anemoside B4 was found to be more efficient in suppressing tumor growth (derived from chemotherapy-resistant HCT116 colorectal cell line) than 5-FU given alone (He et al 2021b). This study provides additional experimental data supporting the potential of triterpene saponins as adjuvants in chemotherapy.…”

Research progress on pharmacological actions and molecular mechanisms of Anemoside B4

“…Li [32] found that the expression of P-gp protein (drug resistance protein) decreased after treatment with non-toxic dose of AB4, which could reverse the drug resistance of human colon cancer L-OHP resistant cells LoVo / L-OHP. He [33] also found that AB4 inhibited the proliferation of human colon cancer HCT116/5-FU cells in vitro and promoted the apoptosis of mouse drug-resistant colorectal cancer cells HCT11/5-FU in vivo. In addition, the combined treatment of AB4 and 5-FU induced the apoptosis of colorectal cancer cells by phosphorylation of Scr protein kinase and activation of caspase-9.…”