Anticancer activity of Hebesu extracts in cancer cell lines

Hebesu, a small citrus fruit from Miyazaki, Japan, has the potential to advance anticancer activity due to its high content of bioactive flavonoids, including narirutin, naringin, hesperidin, and neohesperidin. This study explored the anticancer effects of Hebesu extract (HBS) in various human cancer cell lines: MDA-MB-231 (breast cancer), HepG2 (liver cancer), and A549 (lung cancer). The results showed that treatment with HBS led to a substantial reduction in cell viability in a dose-dependent manner and induced morphological changes, accompanied by increased expression of apoptosis-related markers. TdTomato fluorescence imaging demonstrated that cytotoxicity in breast cancer cells was dependent on both the concentration and duration of exposure. Furthermore, HBS reduced Ki-67 expression, increased the levels of Caspase-3 and NRF2, and downregulated the expression of the oncogenic genes SMO, KRAS, and BRAF. These findings suggest that HBS has a multi-targeted anticancer effect by inhibiting cell proliferation, promoting apoptosis, and activating oxidative stress responses, while also suppressing oncogenic signaling pathways. This study emphasizes the potential use of HBS and its flavonoid components as natural cancer suppressive agents. Further investigation using in vivo models and clinical studies are essential to fully assess their efficacy, bioavailability, and safety.