BW18, a C-21 steroidal glycoside, exerts an excellent anti-leukemia activity through inducing S phase cell cycle arrest and apoptosis via MAPK pathway in K562 cells

Biomed Pharmacother. 2019 Apr:112:108603. doi: 10.1016/j.biopha.2019.108603. Epub 2019 Feb 20.

Abstract

C-21 steroids displayed the activities of immunosuppressive, anti-inflammatory and anti-virus effects by the reports. However, its antitumor effects and molecular mechanism remain unclear. We previously isolated and identified a C-21 steroidal glycoside (BW18) from the root of Cynanchum atratum Bunge. This study was aimed to assess anti-leukemia activity and its underlying mechanism in K562 cells. MTT assay results showed that BW18 inhibited cell viability and proliferation of K562 cells. We also found that BW18 could induce S phase cell cycle arrest and apoptosis. Furthermore, our results demonstrated that BW18 regulated the expression of apoptosis and cell cycle related proteins. Mechanism investigation revealed that the anti-leukemia activity of BW18 may be mediated through MAPK pathway. These findings indicate that BW18 possesses an excellent anti-leukemia activity via regulating MAPK pathway leading to S phase cell cycle arrest and apoptosis, which suggested BW18 could be as a potential alternative therapeutic agent for CML patients.

Keywords: BW18; Cell apoptosis; Cell cycle arrest; Chronic myeloid leukemia; MAPK pathway.

MeSH terms

  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / physiology
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use
  • Glycosides / isolation & purification
  • Glycosides / pharmacology*
  • Glycosides / therapeutic use
  • Humans
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • Phytosterols / isolation & purification
  • Phytosterols / pharmacology*
  • Phytosterols / therapeutic use
  • S Phase / drug effects*
  • S Phase / physiology

Substances

  • Antineoplastic Agents
  • Drugs, Chinese Herbal
  • Glycosides
  • Phytosterols