Stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein respons

Abstract Saturated fatty acids have an anti-proliferative effect on cells. However, there are multiple types of saturated fatty acids, and the effects of each one on cancer cells are not fully elucidated. Here, we explored the effects of palmitate and stearate, saturated fatty acids abundant in the biological systems, on cancer cells. We found that stearate, but not palmitate, had a broad anti-proliferative effect on cancer cell lines originating from multiple organs by causing DNA damage through the unfolded protein response pathway, while oleate mitigated this effect. Feeding an stearate-rich diet and simultaneously inhibiting stearoyl-CoA desaturase-1 activity induced an increase in stearate levels and a decrease in oleate levels in tissues, significantly inhibiting the growth of xenografted ovarian cancer cell lines and patient-derived xenografts. In conclusion, modification of the stearate and oleate dietary composition may have therapeutic significance for cancer.