Panaxydol Derived from Panax ginseng Inhibits G 1 Cell Cycle Progression in Non-small Cell Lung Cancer via Upregulation of Intracellular Ca 2+ Levels

Biol Pharm Bull. 2018;41(11):1701-1707. doi: 10.1248/bpb.b18-00447.

Abstract

Panaxydol, a polyacetylenic compound derived from Panax ginseng has been reported to suppress the growth of cancer cells. However, the molecular mechanisms underlying cell cycle arrest by this compound in non-small cell lung cancer (NSCLC) are unknown. Our study found that panaxydol treatment induced cell cycle arrest at G1 phase in NSCLC cells. The cell cycle arrest was accompanied by down-regulation of the protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E, and decrease in the phosphorylation of retinoblastoma (Rb) protein. Furthermore, up-regulation of cyclin-dependent kinase inhibitor (CDKI) p21CIP1/WAF1 and p27KIP1 was observed in panaxydol-treated NSCLC cells. In addition, panaxydol also induced accumulation of intracellular Ca2+ ([Ca2+]i). (Acetyloxy)methyl 2-({2-[(acetyloxy)methoxy]-2-oxoethyl}[2-(2-{2-[bis({2-[(acetyloxy)methoxy]-2-oxoethyl})amino]phenoxy}ethoxy)phenyl]amino)acetate (BAPTA-AM), the Ca2+ chelator, attenuated not only panaxydol-induced accumulation of [Ca2+]i, but also G1 cell cycle arrest and decrease of CDK6 and cyclin D1 protein expression level. These results demonstrated that the anti-proliferative effects of panaxydol were caused by cell cycle arrest, which is closely linked to the up-regulation of [Ca2+]i and represents a promising approach for the treatment of lung cancer.

Keywords: Panax ginseng; calcium; cell cycle; non-small cell lung cancer; panaxydol.

MeSH terms

  • Calcium / metabolism*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / metabolism
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 6 / metabolism
  • Diynes / pharmacology*
  • Diynes / therapeutic use
  • Fatty Alcohols / pharmacology*
  • Fatty Alcohols / therapeutic use
  • G1 Phase / drug effects*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Oncogene Proteins / metabolism
  • Panax / chemistry*
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Retinoblastoma Protein / metabolism
  • Up-Regulation

Substances

  • CCNE1 protein, human
  • Cell Cycle Proteins
  • Cyclin E
  • Diynes
  • Fatty Alcohols
  • Oncogene Proteins
  • Plant Extracts
  • Retinoblastoma Protein
  • panaxydol
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6
  • Calcium