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Natural products or metabolites from plants and microbes have been recognized as important sources of drug molecules for few decades. Mushrooms offer high sources of new isolable bioactive compounds with diversified chemical structures, which are considered potent sources for drug discovery. The work on potential cancer preventive effects of edible mushrooms, A. bisporus has been less investigated. An attempt has been taken to screen methanolic and ethanolic extract of this mushroom for their anti-cancer potentiality in CaSki cell line. Ethanolic and methanolic extracts of unopened fruit bodies were lyophilized. The different Concentrations of both extracts were used against CaSki cell line for anti-proliferative potentiality by MTT assay. The cell morphological changes of CaSki after treatments with extracts were studied by phase contrast microscope. Nuclear morphology and evaluation of apoptotic cells were studied by DAPI staining under fluorescent microscope. The untreated cells (negative control) exhibited normal elongated shaped and reached 90% confluence after 24 h culture. Cells treated with 100 or 250 µg/mL of ABME are more or less similar to the control cells having elongated shape except few cell numbers. However, cells treated with 500 µg/mL or 750 µg/mL of ABME showed that they became shrink and lose their original shape and the cell confluence was reduced. More round, shrunken cells were observed in cells treated with 500 µg/mL or 750 µg/mL of ABEE while cell culture treated with 1000 µg/mL of ABEE, many cell debris were shown. Nuclei of the untreated CaSki cells were round and homogeneous while nuclei treated with ABME or ABEE nuclei were condensed and in few cases are irregular and fragmented. The evaluation of apoptosis showed that exposure of CaSki cells to different doses of both ABEE and ABME for 24 h resulted in increased apoptosis rates, but ABEE is better than ABME. The MTT assay indicated that maximum concentration 1250 µg/mL of ABEE and ABME showed 83.61±9.98 and 72.44±5.78 % of cell inhibition after 24 h and the IC50 values of these extracts against CaSki were 220 and 490 µg /mL respectively. It indicated that out of the two extracts ABEE was best treatment for inhibition of CaSki cells' proliferation. This report on anti-proliferative and apoptotic effect of A. bisporus on CaSki cell line is probably first time as we go through literature survey.