Phellinus linteus sensitises apoptosis induced by doxorubicin in prostate cancer.
It has been demonstrated that the Phellinus linteus (PL) mushroom, which mainly consists of polysaccharides, possesses antitumour activity. The mechanisms of PL against malignant growth remain unknown. The anticancer drug doxorubicin (Dox) has been shown to induce apoptosis via initiating a caspase cascade. In this investigation, we tested the effect of PL on Dox-induced apoptosis in prostate cancer LNCaP cells. We showed that PL or Dox, at relatively low doses, does not induce apoptosis in the cells. However, combination treatment with low doses of PL and Dox results in a synergistic effect on the induction of apoptosis. In this apoptotic process, caspases 8, 3 and BID are cleaved, and the addition of caspase inhibitor z-VADfmk completely blocks apoptosis. In addition, JNK is activated in response to PL or the combination treatment in LNCaP cells. The suppression of JNK partially inhibits the induction of apoptosis elicited by the co-treatment. These findings indicate that PL has a synergistic effect with Dox to activate caspases in prostate cancer LNCaP cells. Our study also suggests that PL has therapeutic potential to augment the magnitude of apoptosis induced by antiprostate cancer drugs.
Collins
L
L
Department of Pathology, K522, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118, USA.
Zhu
T
T
Guo
J
J
Xiao
Z J
ZJ
Chen
C-Y
CY
D000363:Agaricales / Q000737:chemistry*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000187:drug effects; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D011134:Polysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D011134:Polysaccharides; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D004317:Doxorubicin; D048670:MAP Kinase Kinase 4; D020169:Caspases