Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies.

Background Cancer remains a critical global health challenge and a leading cause of mortality. Flavonoids found in fruits and vegetables have gained attention for their potential anti-cancer properties. Fisetin, abundantly present in strawberries, apples, onions, and other plant sources, has emerged as a promising candidate for cancer prevention. Epidemiological studies linking a diet rich in these foods to lower cancer risk have sparked extensive research on fisetin's efficacy. Objective This review aims to comprehensively explore the molecular mechanisms of fisetin's anticancer properties and investigate its potential synergistic effects with other anticancer drugs. Furthermore, the review examines the therapeutic and preventive effects of fisetin against various cancers. Methods A systematic analysis of the available scientific literature was conducted, including research articles, clinical trials, and review papers related to fisetin's anticancer properties. Reputable databases were searched, and selected studies were critically evaluated to extract essential information on fisetin's mechanisms of action and its interactions with other anticancer drugs. Results Preclinical trials have demonstrated that fisetin inhibits cancer cell growth through mechanisms such as cell cycle alteration, induction of apoptosis, and activation of the autophagy signaling pathway. Additionally, fisetin reduces reactive oxygen species levels, contributing to its overall anticancer potential. Investigation of its synergistic effects with other anticancer drugs suggests potential for combination therapies. Conclusion Fisetin, a bioactive flavonoid abundant in fruits and vegetables, exhibits promising anticancer properties through multiple mechanisms of action. Preclinical trials provide a foundation for further exploration in human clinical trials. Understanding fisetin's molecular mechanisms is vital for developing novel, safe, and effective cancer prevention and treatment strategies. The potential synergy with other anticancer drugs opens new avenues for combination therapies, enhancing cancer management approaches and global health outcomes.

Three New Compounds, Licopyranol A-C, Together with Eighteen Known Compounds Isolated from Glycyrrhiza glabra L. and Their Antitumor Activities.

Glycyrrhiza glabra L., known as licorice, is one of the most famous herbs in the world. In this study, we investigated the phytochemical and antitumor activities of G. glabra, especially its anti-colorectal cancer activities. G. glabra was extracted with 70% methanol, and the ethyl acetate layer was separated by silica gel, ODS, LH-20 column chromatography, and semi-preparative HPLC to obtain the compounds. The structures were determined by NMR and MS methods. Three new compounds named licopyranol A-C (1-3), and eighteen known compounds (4-21) were isolated. Compounds with an isoprenyl group or dimethylpyran ring showed better antitumor activities. Licopyranol A (1) and glycyrol (5) both inhibited the proliferation, reduced clone formation and promoted apoptosis of RKO cells. The Western blotting assays showed that glycyrol significantly reduced the expression of E-cadherin, ß-catenin, c-Myc, and GSK-3ß proteins in RKO cells, suggesting that glycyrol may inhibit the growth of colorectal cancer RKO cells via the Wnt/ß-catenin signaling pathway.

Tamsulosin alters the pharmacokinetics of metformin via inhibition of renal multidrug and toxin extrusion protein 1 and organic cation transporter 2 in rats.

Among the endocrine and metabolic disorders, type-2 diabetes mellitus (T2DM) and benign prostatic hyperplasia (BPH) are common progressive diseases related to aging. Metformin and tamsulosin as the first-choice drug for patients with T2DM and BPH, respectively, are often co-administered to male patients with T2DM and BPH. However, whether concomitantly administering metformin and tamsulosin leads to drug-drug interactions (DDIs) remains unclear. This study aimed to evaluate the effect of tamsulosin on the pharmacokinetics of metformin and explore the relevant underlying mechanism. The plasma, urine, and tissue concentrations of metformin were analyzed using HPLC, and metformin cell uptake was analyzed using LC-MS/MS. In addition, western blotting was used to investigate the expression of Oct1, Oct2, and Mate1. As demonstrated by comparison with metformin alone, tamsulosin significantly increased the area under concentration-time curves (AUC0-t), the maximum plasma concentration (Cmax) and the decreased 24 h cumulative urinary excretion of metformin after single or multiple-dose administration in rats, as well as increased the kidney tissue concentration of metformin after multiple-dose. In addition, tamsulosin treatment significantly inhibited the expression of Mate1 and Oct2 in rat kidneys, but Oct1 and Mate1 did not show a significant difference in the liver. Consistently, tamsulosin inhibited OCT2 and MATE1 expressions and decreased metformin uptake in HEK293 cells. Notably, serum LCA level in the co-administration group was increased by 34% and 39% after multiple-dose (7 and 14 consecutive days, respectively) administration compared to the metformin alone group. Altogether, our data suggest that tamsulosin could increase systemic exposure and reduce excretion of metformin via inhibiting Oct2 and Mate1-mediated transport cooperatively.