Hispolon, a phenolic compound isolated from Phellinus igniarius, induces apoptosis and anti-tumor effects in cancers. However, the molecular mechanism involved in hispolon-mediated tumor-suppressing activities observed in cervical cancer is poorly characterized. Here, we demonstrated that treatment with hispolon inhibited cell metastasis in two cervical cancer cell lines. In addition, the downregulation of the lysosomal protease Cathepsin S (CTSS) was critical for hispolon-mediated suppression of tumor cell metastasis in both in vitro and in vivo models. Moreover, hispolon induced autophagy, which increased LC3 conversion and acidic vesicular organelle formation. Mechanistically, hispolon inhibited the cell motility of cervical cells through the extracellular signal-regulated kinase (ERK) pathway, and blocking of the ERK pathway reversed autophagy-mediated cell motility and CTSS inhibition. Our results indicate that autophagy is essential for decreasing CTSS activity to inhibit tumor metastasis by hispolon treatment in cervical cancer; this finding provides a new perspective on molecular regulation.
FIP-fve is a fungal immunomodulatory protein purified from Flammulina velutipes, an edible golden needle mushroom thought to possess potent immunomodulatory properties. When examined for its effects on lymphocytes, FIP-fve exhibited potent mitogenic effects on human peripheral blood lymphocytes, inducing G1/G0 to S phase proliferation. T cells activated by FIP-fve show significant production and secretion of interferon-gamma (IFN-gamma) associated with intercellular adhesion molecule 1 expression but low detectable levels of interleukin-4 in vitro or in vivo. However, SB203580, the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor, can fully abolish the production of IFN-gamma induced by FIP-fve. At the same time, SB203580 only partially prevents the lymphocytes from progressing from G1 to S phase of the cell cycle. These findings demonstrate that FIP-fve is a potent T-cell activator, mediating its effects via cytokine regulation of p38 MAPK. The immunoprophylatic effects of FIP-fve in Th2-mediated allergic anaphylaxis are believed to be associated with the ability of FIP-fve to enhance activation of IFN-gamma-releasing Th1 cells.
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