Achyranthoside H methyl ester, a novel oleanolic acid saponin derivative from Achyranthes fauriei roots, induces apoptosis in human breast cancer MCF-7 and MDA-MB-453 cells via a caspase activation pathway.

Abstract

Achyranthoside H methyl ester (AH-Me) is an oleanolic acid saponin derivative isolated from the roots of Achyranthes fauriei through diazomethane treatment. AH-Me exhibited significant cytotoxicity against human breast cancer MCF-7 and MDA-MB-453 cells, with respective ID(50) values of 4.0 and 6.5 muM: in the MTT assay. AH-Me is a unique saponin containing three methoxycarbonyl groups in the sugar moiety linked to the C-3 position of oleanolic acid. The demethylation of these methoxycarbonyl groups by alkaline hydrolysis caused a marked reduction of the cytotoxicity of AH-Me, suggesting that the methoxycarbonyl groups of AH-Me are key groups for the acquisition of cytotoxicity against human cancer cells. The staining of cancer cells with 4',6'-diamidino-2-phenylindole (DAPI) showed that the population of cells with altered nuclear morphology, for example chromatin condensation and fragmentation, increased markedly after AH-Me treatment. Exposure of MCF-7 and MDA-MB-453 cells to AH-Me resulted in a dose-dependent and time-dependent increase in the sub-G1 population, and in the cleavage of poly-ADP-ribose polymerase (PARP) followed by the formation of an 89 kD peptide. Pretreatment of the cells with the pan-caspase inhibitor z-VAD-fmk abolished the cleavage of PARP by AH-Me treatment and suppressed the antiproliferative effect of AH-Me on tumor cell growth. These results together led to the suggestion that AH-Me induces apoptosis via the caspase activation pathway in human breast cancer cells, and apoptosis is the major mode of the cytotoxic effect triggered by AH-Me.

• Authors: Motonori Fukumura, Hidehiro Ando, Yasuaki Hirai, Kazuo Toriizuka, Yoshiteru Ida, Yoshiyuki Kuchino
• Journal: Journal of natural medicines (J Nat Med) Vol. 63 Issue 2 Pg. 181-8 (Apr 2009) ISSN: 1861-0293 [Electronic] Japan
• PMID: 19132288 (Publication Type: Journal Article)

Chemical References

• Glucuronides
• Saponins
• achyranthoside H
• Poly(ADP-ribose) Polymerases
• Caspases

Topics

• Achyranthes (chemistry)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, pathology)
• Caspases (drug effects, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Enzyme Activation
• Female
• Glucuronides (administration & dosage, chemistry, isolation & purification)
• Humans
• Hydrolysis
• Inhibitory Concentration 50
• Plant Roots
• Poly(ADP-ribose) Polymerases (drug effects, metabolism)
• Saponins (administration & dosage, chemistry, isolation & purification)
• Time Factors