Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit.
A 70% methanol extract of Terminalia chebula fruit, was studied for its effects on growth in several malignant cell lines including a human (MCF-7) and mouse (S115) breast cancer cell line, a human osteosarcoma cell line (HOS-1), a human prostate cancer cell line (PC-3) and a non-tumorigenic, immortalized human prostate cell line (PNT1A) using assays for proliferation ([(3)H]-thymidine incorporation and coulter counting), cell viability (ATP determination) and cell death (flow cytometry and Hoechst DNA staining). In all cell lines studied, the extract decreased cell viability, inhibited cell proliferation, and induced cell death in a dose dependent manner. Flow cytometry and other analyses showed that some apoptosis was induced by the extract at lower concentrations, but at higher concentrations, necrosis was the major mechanism of cell death. ATP assay guided chromatographic fractionation of the extract yielded ellagic acid, 2,4-chebulyl-beta-D-glucopyranose (a new natural product), and chebulinic acid which were tested by ATP assay on HOS-1 cell line in comparison to three known antigrowth phenolics of Terminalia, gallic acid, ethyl gallate, luteolin, and tannic acid. Chebulinic acid (IC(50) = 53.2 microM +/- 0.16) > tannic acid (IC(50) = 59.0 microg/ml +/- 0.19) > and ellagic acid (IC(50) = 78.5 microM +/- 0.24), were the most growth inhibitory phenolics of T. chebula fruit in our study.
Saleem
Ammar
A
Department of Chemistry, University of Turku, Kiinamyllynkatu 10, FIN-20014 Turku, Finland. amsale@utu.fi
Husheem
Michael
M
Härkönen
Pirkko
P
Pihlaja
Kalevi
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D051379:Mice; D015394:Molecular Structure; D009336:Necrosis; D009369:Neoplasms / Q000473:pathology*; D012516:Osteosarcoma / Q000473:pathology; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology; D029766:Terminalia / Q000737:chemistry*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D010636:Phenols; D010936:Plant Extracts; D000255:Adenosine Triphosphate