Toshihiko Fukamachi, Hiromi Saito and Hiroshi Kobayashi
Many clinical investigations have suggested that statins are useful chemotherapeutics against various cancers, whereas in vitro experiments using cancer cell lines have shown little effect of statins on cell proliferation and survival. Our group previously demonstrated that statins were preferentially cytotoxic against HeLa, mesothelioma, and pancreatic tumor cells under acidic conditions. A serious side effect of anti-cancer drugs used now is the impairment of the immune system. In this study, we examined the effect of simvastatin on the immune cell lines THP-1 and Jurkat in alkaline and acidic media. Our data suggest that simvastatin inhibited proliferation, survival, and cytokine production at an acidic pH in these cells, whereas the inhibitory effect was negligible at an alkaline pH. These results suggest that anti-cancer drugs whose efficacy increases in acidic cancer nests are useful for potent chemotherapeutics against cancer without causing serious damage to the immune cells in blood and normal tissues, whose pH is slightly alkaline, although the functions of immune cells that have infiltrated acidic cancer nests may be attenuated.
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