Bavachin induces apoptosis in colorectal cancer cells through Gadd45a via the MAPK signaling pathway

Chin J Nat Med. 2023 Jan;21(1):36-46. doi: 10.1016/S1875-5364(23)60383-8.

Abstract

Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia, and exhibits anti-bacterial, anti-inflammatory, anti-tumor and lipid-lowering activities. Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines. However, the anti-cancer effects and related mechanisms in colorectal cancer remain unknown. Here, we investigated the effects of bavachin on colorectal cancer in vivo and in vitro. The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis. These changes were mediated by activating the MAPK signaling pathway, which significantly up-regulated the expression of Gadd45a. Furthermore, Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis. Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin. The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer. In conclusion, these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.

Keywords: Apoptosis; Bavachin; Colorectal cancer; Gadd45a; MAPK.

MeSH terms

  • Apoptosis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Flavonoids / pharmacology
  • Humans
  • MAP Kinase Signaling System
  • Proteins / metabolism
  • Proteins / pharmacology
  • Signal Transduction*

Substances

  • bavachin
  • Flavonoids
  • Proteins
  • GADD45A protein, human
  • Cell Cycle Proteins