Anticancer effect of total annonaceous acetogenins on hepatocarcinoma

Chin J Integr Med. 2015 Sep;21(9):682-8. doi: 10.1007/s11655-014-1845-z. Epub 2014 Jun 18.

Abstract

Objective: To confirm the anticancer effect of total annonaceous acetogenins (TAAs) abstracted from Annona squamosa Linn. on human hepatocarcinoma.

Methods: The inhibitory effect of TAAs was demonstrated in H22-bearing mice. The potency of TAAs was confirmed as its 50% inhibiting concentration (IC50) on Bel-7402 cell under Sulfur Rhodamine B staining. Both underlying mechanisms were explored as cellular apoptosis and cell cycle under flow cytometry. Mitochondrial and recipient apoptotic pathways were differentiated as mitochondrial membrane potential under flow cytometry and caspases activities under fluorescence analysis.

Results: The inhibitory rate of TAAs in mice was 50.98% at 4 mg/kg dose. The IC50 of TAAs on Bel-7402 was 20.06 µg/mL (15.13-26.61µg/mL). Effective mechanisms of TAAs were confirmed as both of arresting cell cycle at G1 phase and inducing apoptosis dose- and time-dependently. Mitochondrial and recipient pathways involved in apoptotic actions of TAAs.

Conclusion: TAAs is effective for hepatocarcinoma, via inhibiting proliferation and inducing apoptosis.

Keywords: annonaceous acetogenins; apoptosis; hepatocarcinoma; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetogenins / chemistry
  • Acetogenins / pharmacology
  • Acetogenins / therapeutic use*
  • Animals
  • Annona / chemistry*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / pathology
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Organ Specificity / drug effects
  • Spleen / drug effects
  • Thymus Gland / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Acetogenins
  • Antineoplastic Agents, Phytogenic
  • Caspases