Anticancer Potential of Compounds from an Edible Mushroom, Lentinus tuberregium (Fr. ) Fr.

摘要

The search for new anti-cancer compounds in mushrooms is one realistic and promising approach to prevention. The growth inhibitory effects of two compounds-LT1 and LT2 isolated from an edible mushroom Lentinus tuberregium were tested in a panel of cancer cell lines viz., SK-OV-03 (ovarian cancer) , A673 (Rhabdomyosarcoma), HCT-116 (colorectal carcinoma) and MCF (breast cancer) and the viability of cells was determined by MTT assay. Further, the anticancer potential of LT1 and LT2 at three different semilogarithmic concentrations viz., 3, 10, 30 μM in A673 cells exposed for 24 and 48 h was evaluated by flow cytometry. Apoptotic induction was confirmed by confocal microscopy, based on the nuclear morphology by PI staining. Of the four cancer lines tested, both LT1 and LT2 exerted maximal growth inhibition in SK-OV-03,followed by A673. On the other hand, HCT-116 showed moderate growth inhibition. Comparatively, LT1 was more potent in causing cell growth inhibition than LT2 in A673 cancer cell line. Surprisingly, LT2 did not inhibit cell proliferation in MCF-7 cell line. Exposure of LT1 at 3 and 10 μM concentration for 24 h caused a G2-M arrest. At 10 μM concentration, cells also accumulated in G0-G1 phase, indicating a G1 block. These effects were only transient as prolonged exposure (48 h) of LT1 treatment brought back the cell population to normalcy. Exposure of LT2 for 24 h resulted in a concentrationdependent phenotype in A673 cells. LT2 at 3 μM concentration, arrested the cells primarily in G2-M phase. With 10 μM concentration, cells evidenced G0-G1 arrest. At 30 μM concentration of both LT1 and LT2, cell population in G0-G1, S and G2-M phases decreased with a corresponding increase in cell population in sub G0-G1. Both the compounds only at this concentration have the potential to induce a hypodiploid peak (sub GO), indicating an induction of apoptosis. Apoptotic induction was explicit by membrane blebbing, mitotic catastrophe, and fragmentation of nuclei in cells exposed to 30 μM concentration of LT1 and LT2. Apoptotic induction was further confirmed by caspase activity, which was dose-dependent and compoundspecific. Caspase activity was higher in LT2 as compared to LT1. In conclusion, the overall findings of the present study shed light on the growth inhibitory activity as determined by MTT assay and anticancer potential of LT1 and LT2 by flow cytometry and confocal microscopy to identify possible targets for cancer intervention.