Montmorillonite (Mt) nanosheets are used in pharmaceutical products as both excipient and active ingredients. In addition, Mt can be used as a nanocarrier for oral delivery of drugs, including chemotherapy drugs, and as an embolic agent for tumor arterial embolization. It is noteworthy that, there is few conflicting evidence on the intrinsic antitumor activity of Mt. Hence, in this study, the antitumor potential of Mt was investigated using MRC-5, HT-29 and HepG2 cell lines. MTT assay revealed that, Mt possesses antiproliferative effect, which was concentration-dependent and affected by both protein level and cell type. However, this antiproliferative effect was not significantly affected by increasing the exposure time from 24 to 48 h. The results of flow-cytometry and qRT-PCR analyses showed that, Mt induced G0/G1-phase arrest in MRC-5 and HT-29 cells by modulating P21, P27 and Cyclin D1 genes, whereas it induced S-phase arrest in HepG2 cells probably by damaging DNA and up-regulating mTOR gene. The results also indicated that, Mt induced a high rate of apoptosis in all the cell lines by modulating anti/pro-apoptotic genes, as well as a rate of necrosis in HT-29. The apoptosis of MRC-5 and HT-29 cells was accompanied with up-regulation of P62 gene, suggesting autophagy-dependent apoptosis. In addition, in all the cell lines, Mt significantly enhanced the expression of executioner caspase-3. Based on these results, the biocompatible Mt nanosheets can act as antitumor agents. These findings may provide new applications of Mt in the field of cancer therapy.
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