Antitumor activity of asukamycin, a secondary metabolite from the actinomycete bacterium Streptomyces nodosus subspecies asukaensis.
Asukamycin, a manumycin-type metabolite, was isolated by a rapid and easily scalable purification scheme. Thus far, studies on the biological activity of asukamycin have been limited to its role as an antibacterial and antifungal agent. By using five different tumor cell lines we demonstrate antineoplastic activity of asukamycin. It inhibited cell growth at concentrations similar to other members of the manumycin family (IC50 1-5 microM). Cytotoxicity of asukamycin was accompanied by activation of caspases 8 and 3 and was diminished by SB 202190, a specific p38 mitogen-activated protein kinase (MAPK) inhibitor. These data, in combination with earlier observations showing its low in vivo toxicity, indicate that further studies on the potential antitumor activity of asukamycin are warranted.
Department of Chemistry, Irving K. Barber School of Arts and Sciences, University of British Columbia Okanagan, Kelowna, BC, V1V 1V7, Canada.
Paul R
PR
Shipley
Caitlin C A
CC
Donnelly
Cuong H
CH
Le
Ashley D
AD
Bernauer
Andis
A
Klegeris
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011090:Polyenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000737:chemistry; D013302:Streptomyces / Q000737:chemistry*
D000970:Antineoplastic Agents; D011090:Polyenes; D053284:Polyunsaturated Alkamides; C013404:asukamycin; D053148:Caspase 3; D053181:Caspase 8; C054474:manumycin