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ABSTRACT: Protein-bound polysaccharide-K (PSK) is extracted from Coriolus versicolor (CM101). PSK is a biological response modifier (BRM), and its mechanism of action is partly mediated by modulating host immune systems; however, recent studies showed antiproliferative activity of PSK. Therefore, we examined the mechanism underlying the antiproliferative activity of PSK using seven different human malignant cell lines (WiDr, HT29, SW480, KATOⅢ, AGS, HL-60 and U937), and PSK was found to inhibit the proliferation of HL-60 cells most profoundly. Therefore, HL-60 cells were used to elucidate the mechanism of the antiproliferative activity. Western blotting was performed to detect phosphorylated p38 mitogen-activated protein kinase (MAPK). A p38 MAPK inhibitor, SB203580, was used to examine the roles in PSK-induced apoptosis and growth inhibition. Flow cytometry was performed for mitochondrial membrane potential detection. PSK activated caspase-3 and induced p38 MAPK phosphorylation. Co-treatment with SB203580 blocked PSK-induced apoptosis, caspase-3 activation and growth inhibition. PSK induced apoptosis via the mitochondrial pathway. The depolarization of mitochondria induced by PSK was reversed by co-treatment with SB203580. The present study revealed that PSK induced apoptosis in HL-60 cells via a mitochondrial and p38 MAPK-dependent pathway.
Oncology Reports 04/2013; · 1.84 Impact Factor
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ABSTRACT: Protein-bound polysaccharide-K (PSK) is extracted from Coriolus versicolor (CM101) and is clinically used in combination therapy for gastrointestinal cancer and small-cell lung carcinoma. We have previously demonstrated that PSK induces apoptosis and inhibites proliferation of promyelomonocytic leukemia HL-60 cells, but the signaling pathway for this action remains to be elucidated. In HL-60 cells, the mitogen-activated protein kinase (MAPK) pathway has been reported to be involved in stimuli-induced apoptosis. Therefore, involvement of the p38 MAPK pathway in PSK-induced apoptosis was herein investigated.
HL-60 cells were used in this study. Western blotting was performed to detect phosphorylated p38 MAPK. A p38 MAPK inhibitor, SB203580, was used to examine the roles of p38 MAPK in PSK-induced apoptosis and growth inhibition.
PSK induced p38 MAPK phosphorylation. Co-treatment with SB203580 blocked PSK-induced apoptosis, caspase-3 activation and growth inhibition.
The p38 MAPK pathway plays an important role in PSK-induced apoptosis.
Anticancer research 07/2012; 32(7):2631-7. · 1.73 Impact Factor
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ABSTRACT: Previously, we reported that PSK induces apoptosis and growth inhibition in HL60 cells. In this study, we tried to clarify the mechanism of how PSK induces apoptosis. Because several reports suggested that apoptosis of HL60 cells is mediated by activation of p38MAPK, we examined whether p38MAPK is involved in PSK-induced apoptosis. First, we found that PSK induced p38MAPK phosphorylation, which is considered as its activation. Next, we demonstrated that SB203580, inhibitor of p38MAPK, inhibited PSK-induced apoptosis. These results suggest that p38MAPK plays an important role in PSK-induced apoptosis.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2011; 38(12):1915-7.
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ABSTRACT: Protein-bound polysaccharide-K (PSK) is extracted from Coriolus versicolor (CM101), and is clinically used in combination therapy for gastrointestinal cancer and small cell lung carcinoma. PSK is a biological response modifier (BRM), and its mechanism of action is partly mediated, by modulating host immune systems, such as the activation of immune effector cells and the neutralization of transforming growth factor-beta (TGFβ) activity. Direct inhibition of tumor cell proliferation has been reported as another mechanism, but how PSK induces such an effect remains to be elucidated. Here, the anti-proliferative activity of PSK was examined using seven different human malignant cell lines (WiDr, HT29, SW480, KATOIII, AGS, HL60 and U937), and PSK was found to inhibit the proliferation of HL-60 cells most profoundly. Therefore, HL-60 cells were used to clarify the mechanism of anti-proliferative activity. Caspase-3 activation followed by apoptosis are involved at least in part in the PSK-induced anti-proliferative activity against HL-60 cells.
Anticancer research 09/2011; 31(9):2733-8. · 1.73 Impact Factor
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ABSTRACT: Although PSK is an antitumor drug with immunomodulating effects, it has also been shown to have a direct action on cancer cells. This study analyzed the mechanism of the direct action of PSK on cancer cells, focused on the apoptosis-inducing effect. First, the cell growth inhibitory effect of PSK was examined using seven cancer cell lines, and HL60 cells were found to be strongly inhibited. Next, using HL60 cells, the apoptosis-inducing effect of PSK was examined using Annexin-V/Propidium iodide immunostaining and DNA fragmentation. The results indicated that PSK induced the apoptosis of HL60 cells. When the effect of PSK on protein expression of apoptosis-related factors was analyzed using an apoptosis array, over-expression of pro-caspase-3 and under-expression of factors such as cIAP-1, and cIAP-2 were observed. Furthermore, FACS analysis confirmed an increase in percentage of cells expressing activated caspase-3. These findings suggest that PSK induces apoptosis of HL60 cells and inhibits cell proliferation.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(12):2255-7.
