Intracellular Ca2+ release mediates ursolic acid-induced apoptosis in human leukemic HL-60 cells

Int J Cancer. 1997 Nov 27;73(5):725-8. doi: 10.1002/(sici)1097-0215(19971127)73:5<725::aid-ijc19>3.0.co;2-4.

Abstract

The effect of ursolic acid (UA) on tumor cell apoptosis was investigated using HL-60 human promyelocytic leukemia cells as a model cellular system. Treatment with UA resulted in a concentration-dependent decreased cell viability assessed by MTT assay. UA also induced genomic DNA fragmentation, a hallmark of apoptosis, indicating that the mechanism by which UA induced cell death was through apoptosis. The intracellular Ca2+ level was increased by treatment with UA. Intracellular Ca2+ inhibitors, such as intracellular Ca2+-release blockers (dantrolene, TMB-8 and ruthenium red) and an intracellular Ca2+ chelator (BAPTA/AM), significantly blocked the UA-induced increased intracellular Ca+ concentration. These inhibitors also blocked the effects of UA on cell viability and apoptosis. These results suggest that enhanced intracellular Ca2+ signals may be involved in UA-induced apoptosis in HL-60 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / antagonists & inhibitors
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Cell Survival / drug effects
  • DNA Fragmentation / drug effects
  • DNA, Neoplasm / drug effects
  • Dose-Response Relationship, Drug
  • HL-60 Cells / drug effects
  • HL-60 Cells / metabolism*
  • HL-60 Cells / pathology
  • Humans
  • Triterpenes / antagonists & inhibitors
  • Triterpenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Calcium Channel Blockers
  • DNA, Neoplasm
  • Triterpenes
  • ursolic acid
  • Calcium