title: Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types.
abstract: Betulinic acid (BA) is a widely available plant-derived triterpene with reported activity against cancer cells of neuroectodermal origin and leukaemias. Treatment with BA was shown to protect mice against transplanted human melanoma and led to tumor regression. In contrast, cells from healthy tissues were resistant to BA and toxic side-effects in animals were absent. These findings have raised interest in the chemotherapeutical anti-cancer potential of BA. A comprehensive assessment of the efficacy of BA against the clinically most important cancer types is currently lacking. Therefore, we tested the in vitro sensitivity of broad cell line panels derived from lung, colorectal, breast, prostate and cervical cancer, which are the prevalent cancer types characterized with highest mortalities in woman and men. Multiple assays were used in order to allow a reliable assessment of anti-cancer efficacy of BA. After 48 h of treatment with BA, cell viability as assessed with MTT and cell death as measured with propidium iodide exclusion showed clear differences in sensitivity between cell lines. However, in all cell lines tested colony formation was completely halted at remarkably equal BA concentrations that are likely attainable in vivo. Our results substantiate the possible application of BA as a chemotherapeutic agent for the most prevalent human cancer types.
authors.affiliation: Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Kessler
authors.forename: Franziska B
authors.initials: FB
authors.lastname: Mullauer
authors.forename: Guido M
authors.initials: GM
authors.lastname: de Roo
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Medema
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053978:Pentacyclic Triterpenes; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014315:Triterpenes / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000094062:Betulinic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D011065:Poly(ADP-ribose) Polymerases; D000094062:Betulinic Acid