Atractylenolide III induces apoptosis by regulating the Bax/Bcl-2 signaling pathway in human colorectal cancer HCT-116 Cells in vitro and in vivo

Anticancer Drugs. 2022 Jan 1;33(1):30-47. doi: 10.1097/CAD.0000000000001136.

Abstract

Atractylodes is the dry root of atractylodes macrocephala koidz and has been commonly used as a traditional Chinese medicine (TCM). Atractylenolide III, a main component of atractylodes, has displayed significant effects on anti-inflammation and anticancer. However, the effects of atractylenolide III on growth inhibition and apoptosis induction in colon cancer remain unclear. The results showed that atractylenolide III significantly inhibited the cell growth and induce cellular apoptosis in HCT-116 cells in a concentration dependence manner in vitro. Mechanistic studies further showed that atractylenolide III could regulate the Bax/Bcl-2 apoptotic signaling pathway through promoting the expression of proapoptotic related gene/proteins Bax, caspase-9 and caspase-3 but inhibiting the expression of antiapoptotic related gene/protein Bcl-2 in HCT-116 cells. Furthermore, atractylenolide III also significantly inhibited the tumor growth of HCT-116 tumor xenografts bearing in nude mice through inducing apoptosis by upregulation of the expressions of Bax, cleaved caspase-3 and p53 but downregulation of the expressions of Bcl-2 in HCT-116 tumor tissues in vivo. The studies may provide the scientific rationale for the understanding of the anticancer effect of atractylenolide III. Therefore, atractylenolide III may have the potential to be developed as a promising novel anticancer agent for the treatment of colorectal cancer clinically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / drug effects
  • Caspase 9 / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / pathology*
  • Dose-Response Relationship, Drug
  • Humans
  • Lactones / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Proto-Oncogene Proteins c-bcl-2 / drug effects*
  • Rats
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / drug effects*

Substances

  • BCL2 protein, human
  • Lactones
  • Proto-Oncogene Proteins c-bcl-2
  • Sesquiterpenes
  • atractylenolide III
  • bcl-2-Associated X Protein
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9