Alisol B-23-acetate, a tetracyclic triterpenoid isolated from Alisma orientale, induces apoptosis in human lung cancer cells via the mitochondrial pathway

Biochem Biophys Res Commun. 2018 Nov 10;505(4):1015-1021. doi: 10.1016/j.bbrc.2018.10.022. Epub 2018 Oct 9.

Abstract

Alisol B-23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale, has been reported to exert anti-proliferative activities in human colon, ovarian and gastric cancer cells. However, the anti-cancer effect of this compound on human lung cancer cells has not yet been thoroughly elucidated. In the present study, we investigated the effects of AB23A on the cell viability and apoptosis in human lung cancer A549 and NCI-H292 cells. The results indicated that AB23A inhibited the growth of A549 and NCI-H292 cells in dose- and time-dependent manner, however, there was only weak cytotoxicity on normal bronchial epithelial cells. The induction of apoptosis by AB23A was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed that AB23A decreased mitochondrial membrane potential (MMP) and up regulated reactive oxygen species (ROS) level. Meanwhile, the increased Bax/Bcl-2 ratio, activated caspase-3, caspase-9 and PARP were observed. In addition, AB23A increased the release of cytochrome c from mitochondria and the translocation of apoptotic inducing factor (AIF) into nuclei. Taken together, these results indicated that AB23A induced apoptosis by activating the intrinsic pathway, and suggested that AB23A can be used as a potential modulating agent in lung cancer.

Keywords: Alisol B-23-acetate; Lung cancer; Tetracyclic triterpenoid; apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alisma / chemistry*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Cholestenones / chemistry
  • Cholestenones / isolation & purification
  • Cholestenones / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Molecular Conformation
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Cholestenones
  • alisol B 23-acetate