Methanolic Extract of the Nutritional Plant (Diospyros kaki Thunb.) Exhibits Anticancer Activity by Inducing Mitochondrial Dysfunction in Colorectal Cancer Cells

<b>Background/Objectives:</b><i>Diospyros kaki</i>, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves' extracts contain high amounts of flavonoids and terpenoids, endowed with several beneficial effects. However, its anticancer activity towards colorectal cancer (CRC) has not been investigated in depth. <b>Methods:</b> The effect of a methanolic extract of <i>D. kaki</i> leaves, rich in kaempferol and quercetin derivatives, have been evaluated on an E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS-activating mutation. <b>Results:</b> This extract is effective in reducing tumor cells' viability without affecting the healthy mucosa cell line CCD 841. In fact, Western blot experiments showed its ability to induce apoptosis in cancer cells by increasing oxidative stress and disrupting mitochondrial functionality, as shown by reactive oxygen species measurement and Seahorse analysis. <b>Conclusions:</b> With the aim of increasing healthspan, as well as the substantial societal and macroeconomic costs associated with cancer, our results could pave the way to a role for <i>D. kaki</i> extract in both CRC treatment and prevention.