Hormetic Effects of Hormones, Antihormones, and Antidepressants on Cancer Cell Growth in Culture: In Vivo Correlates

Evidence is presented that the ability of hormones and antihormones to cause biphasic (hormetic) proliferative responses in cancer cells in vitro correlates with a similar effect of these substances in humans with cancer. Certain antidepressants also produce biphasic growth responses of cancer cells in vitro and stimulate cancer growth in rodents, correlating with an increased risk of breast and other cancers in some, but not all, epidemiological studies assessing early and/or late cancer incidence in patients on antidepressant drugs. The observation that certain drugs with biphasic effects on cancer cell growth in vitro may also produce an “up–down” effect on cancer growth in humans supports Calabrese's suggestion that the concept of the hormetic dose response must be taken seriously by toxicologists and regulators.