In Vitro Evaluation of 4-Methoxyresorcinol and Kaempferol 7-ORutinoside and Their Radioiodinated Derivatives in MCF-7, MDA-MB-231, and LNCaP Cell Lines

The global population is currently experiencing high rates of mortality due to the growing burden of cancer. Efforts on the development of new potent anticancer agents are necessary. Therefore, this study aimed to evaluate the anticancer activity of two flavonoids, including 4-methoxyresorcinol (MRC) and kaempferol 7-O-rutinoside (K7R), isolated from Melia azedarach L. leaves. Anticancer activity was evaluated in vitro against MCF-7, MDA-MB-231, and LNCaP cell lines. Radioiodination was performed with iodine-131 as well as computational studies to assess the feasibility of the isolated compounds as natural product-based radiopharmaceuticals for diagnosing and managing cancer. The results showed that MRC and K7R had moderate anticancer activity against MCF-7, MDA-MB-231, and LNCaP cell lines with IC50 values ranging from 154.75 to 1962.66 µM. Cellular uptake investigations found that the highest cellular accumulation of [131I]-4-methoxyresorcinol (MRCI) was observed in MCF-7 (3.17 ± 0.11%) after 24 hours of incubation, approximately 20-fold greater than the control group uptake (iodine-131). Meanwhile, [131I]-kaempferol 7-O-rutinoside (K7RI) showed the highest uptake in MCF-7 (3.05 ± 0.9%) post-one hour of incubation, which was around 23-folds higher than iodine-131 uptake. In conclusion, both MRC and K7R were identified as potential anticancer drugs, which could be further developed into new radiopharmaceutical candidates.