title: In vitro anti-cancer activity of a novel microbial fermentation product on human carcinomas.
abstract: The possible anti-proliferation and cell death induction potential of a novel microbial fermentation extract named as oncogen XP-180 (or simply as XP-180) was tested on three human solid tumour carcinoma cell lines (non-small cell lung cancer A549, breast cancer MDA-MB231, liver adenocarcinoma SK-Hep1) and on the acute myelogenous leukaemia KG1a cell line. Anti-proliferative activity of XP-180 was observed on all of these cancer cell lines with comparable efficiency and in a dose-dependent manner. Morphological investigation further suggested that common features of apoptosis, including cell shrinkage and rounding, are present in XP-180 treated cells. Loss of adhesion properties of these solid tumour cell lines was observed upon XP-180 incubation. Anchorage-dependent clonogenicity assay on solid tumour cell lines and semi-solid methylcellulose colony formation assay on leukaemia cell line further revealed that XP-180 strongly inhibited the regeneration potential of these cancer cells. Using KG1a as an experimental model system, XP-180 was shown to stimulate the activity of caspase 3, 8 and 9 without significant change in caspase 6 activity. Furthermore, XP-180 readily induced collapse of mitochondrial membrane potential after 2 h of incubation. However, the use of the generic caspase specific inhibitor Z-VAD-FMK does not significantly reverse XP-180 mediated cell death. The results obtained suggest that XP-180-mediated cancer cell death could involve mitochondria and both caspase-dependent and -independent pathways. Therefore, XP-180 is an efficient anti-cancer regimen in vitro.
authors.affiliation: Anti-Cancer Research Center, State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology, and Chemical Technology, The Hong Kong Polytechnic University, PR China.
authors.forename: Chung Hin
authors.initials: CH
authors.lastname: Chui
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Fung Yi
authors.initials: FY
authors.lastname: Lau
authors.forename: Gregory Yin Ming
authors.initials: GY
authors.lastname: Cheng
authors.forename: Raymond Siu Ming
authors.initials: RS
authors.lastname: Wong
authors.forename: Stanton Hon Lung
authors.initials: SH
authors.lastname: Kok
authors.forename: Johnny Cheuk On
authors.initials: JC
authors.lastname: Tang
authors.forename: Ivy Tuang Ngo
authors.initials: IT
authors.lastname: Teo
authors.forename: Filly
authors.initials: F
authors.lastname: Cheung
authors.forename: Chor Hing
authors.initials: CH
authors.lastname: Cheng
authors.forename: Kwok Ping
authors.initials: KP
authors.lastname: Ho
authors.forename: Albert Sun Chi
authors.initials: AS
authors.lastname: Chan
authors.forename: Alfonso
authors.initials: A
authors.lastname: Wong
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001419:Bacteria / Q000737:chemistry* / Q000378:metabolism; D001688:Biological Products / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005285:Fermentation; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000502:physiology; D014410:Tumor Stem Cell Assay
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D001688:Biological Products; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases