Pro-apoptotic and immunomodulatory activity of a mycobacterial cell wall-DNA complex towards LNCaP prostate cancer cells.
BACKGROUND
We have isolated a mycobacterial cell wall-DNA complex (MCC) possessing anti-cancer activity against bladder cancer cells. The anti-cancer activity of MCC appears to be due to two effects: a direct interaction with bladder cancer cells resulting in the induction of apoptosis and an indirect effect via the stimulation of monocytes and macrophages cytokine synthesis. In this study, the direct effect of MCC towards LNCaP cancer cells was evaluated.


METHODS
Inhibition of proliferation, cell cycle arrest and induction of apoptosis were evaluated in vitro using LNCaP cells treated with MCC. The synthesis of IL-12, GM-CSF, and TNF-alpha by LNCaP cells in response to MCC was also determined. Experiments were performed to gain insight into the mechanism of action of MCC towards LNCaP cells.


RESULTS
MCC caused a dose-dependent inhibition of the proliferation of LNCaP cells that was associated with cell cycle arrest at the G0/G1 phase. MCC-induced apoptosis of LNCaP cells was consistent with a mitochondrial pathway involving mitochondrial disruption, release of cytochrome c, and an increase in Bax protein levels leading to caspase-3 and -7 activation and cleavage of poly (ADP-ribose) polymerase and nuclear mitotic apparatus protein. Surprisingly, MCC also directly induced the synthesis of IL-12 and GM-CSF, but not TNF-alpha, by LNCaP cells.


CONCLUSIONS
MCC possesses the ability to directly induce apoptosis of LNCaP cells and to trigger the synthesis of IL-12 and GM-CSF by these cells, suggesting a potential role of MCC for the treatment of prostate cancer.
Reader
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Bioniche Therapeutics Research Centre, Montréal, Québec, Canada.
Ménard
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S
Filion
B
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Filion
M C
MC
Phillips
N C
NC
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002473:Cell Wall / Q000737:chemistry; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D004269:DNA, Bacterial / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009168:Mycobacterium phlei / Q000737:chemistry*; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D004269:DNA, Bacterial; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases