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

Abstract Fatty acids are known to have a significant impact on the properties of cancer cells. Therefore, Incorporating them into therapeutic strategies has been reported. However, few studies have examined the effects of individual fatty acids and their interaction in depth. The study analyzed the effects of various fatty acids on cancer cells and found that stearic acid, an abundant saturated fatty acid, had a stronger inhibitory effect on cell growth compared to palmitic acid, which is also an abundant saturated fatty acid, by inducing DNA damage and apoptosis through the unfolded protein response (UPR) pathway. Intriguingly, the negative effects of stearate were reduced by the presence of oleate, a different type of abundant fatty acid. In exploring the dietary impact on tumor growth, we combined a stearate-rich diet with the inhibition of stearoyl-CoA desaturase-1. This approach significantly reduced tumor growth in both ovarian cancer models and patient-derived xenografts (PDXs), including those with chemotherapy-resistant cases, by notably elevating stearate levels while reducing oleate levels within the tumors. Conversely, the negative effects of a stearate-rich diet were mitigated by an oleate-rich diet. The study shows that the dietary stearate can directly inhibit tumor growth through mechanisms involving DNA damage and apoptosis mediated by the UPR pathway. The results suggest that dietary interventions, which increase stearic acid levels while decreasing oleic acid levels, may be a promising therapeutic strategy in cancer treatment. This could lead to the development of new cancer treatment strategies.