Tumor cell growth inhibition by several Annonaceous acetogenins in an in vitro disk diffusion assay.
The cell inhibition activities of several Annonaceous acetogenins, covering the three major structural classes of bis-adjacent, bis-non-adjacent, and single tetrahydrofuran (THF) ring compounds and their respective ketolactone rearrangement products, were tested in an in vitro disk diffusion assay against three murine (P388, PO3, and M17/Adr) and two human (H8 and H125) cancerous cell lines as well as a non-cancerous immortalized rat GI epithelial cell line (I18). The results demonstrate a dose-dependent inhibition of cancerous cell growth, while non-cancerous cell growth is not inhibited by the same dosages. All of the acetogenins, irrespective of their various structural types, inhibit the growth of adriamycin resistant tumor cells and non-resistant tumor cells at the same levels of potency. These results show that the Annonaceous acetogenins are an extremely potent class of compounds, and their inhibition of cell growth can be selective for cancerous cells and also effective for drug resistant cancer cells, while exhibiting only minimal toxicity to 'normal' non-cancerous cells.
Oberlies
N H
NH
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907-1333, USA.
Jones
J L
JL
Corbett
T H
TH
Fotopoulos
S S
SS
McLaughlin
J L
JL
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D006131:Growth Inhibitors; D007783:Lactones; C018674:tetrahydrofuran