In vitro anti-cancer activity of a novel microbial fermentation product on human carcinomas.
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.
Chui
Chung Hin
CH
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.
Gambari
Roberto
R
Lau
Fung Yi
FY
Cheng
Gregory Yin Ming
GY
Wong
Raymond Siu Ming
RS
Kok
Stanton Hon Lung
SH
Tang
Johnny Cheuk On
JC
Teo
Ivy Tuang Ngo
IT
Cheung
Filly
F
Cheng
Chor Hing
CH
Ho
Kwok Ping
KP
Chan
Albert Sun Chi
AS
Wong
Alfonso
A
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
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