2024 Volume 77 Issue 6 Pages 431-438
Tamoxifen (TAM) has been used universally for the treatment of estrogen-sensitive breast cancer, but it is also known to decrease the count of cells such as leukocytes by induction of off-target apoptosis. In this study, we examined the effects of lipids, a biological component related to the cytotoxicity of TAM, by observing apoptosis in monocytic leukemia cells (U937 cells) cultured in the presence of palmitic acid (PA), a saturated fatty acid. PA significantly suppressed TAM-induced apoptosis in U937 cells in terms of DEVDase activity and nuclear aggregation/fragmentation. In contrast, oleic acid (OA) had a weaker inhibitory effect. In addition, 17β-estradiol (E2) had no effect on apoptosis induced by TAM, nor did it induce apoptosis on its own. Mitochondrial analysis revealed that PA suppressed TAM-induced inhibition of respiratory chain complex I and II (CI, II) activity. These results suggest that PA may reduce the estrogen receptor (ER) -independent cytotoxicity of TAM.
