Tumor-suppressive zinc finger protein 24 (ZNF24) sensitizes colorectal cancer cells to 5-fluorouracil by inhibiting the Wnt pathway and activating the p53 signaling.

Carcinogenesis and colorectal cancer (CRC) development are associated with dysregulation of various pathways, including Wnt and p53. 5-fluorouracil (5-FU) is a common chemotherapeutic agent for CRC treatment, but its efficacy is restricted by drug resistance. Doxycycline is an orally active tetracycline antibiotic known for its antimicrobial and anticancer cell proliferation activities. This study intends to delineate the potential role of bioinformatically predicted ZNF24 in the 5-FU resistance of CRC cells. The expression of ZNF24 was measured in clinically collected CRC tissues and cells. Afterward, ectopic ZNF24 expression was induced by DOX to evaluate the viability, colony-forming ability and sphere-forming ability of CRC cells. It was found that ZNF24 was validated to be poorly expressed in CRC tissues, and ectopic expression of ZNF24 was revealed to restrict the malignant phenotypes of CRC cells. In addition, restored ZNF24 attenuated 5-FU resistance of CRC cells by inhibiting the Wnt pathway and activating p53 signaling. Furthermore, an inhibitor of Wnt production 2 (IWP-2) treatment was an alternative to ZNF24 up-regulation in sensitizing CRC cells to 5-FU treatment. In conclusion, our results indicate that ZNF24 inhibits 5-FU resistance of CRC cells by suppressing the Wnt pathway and activating p53 signaling, which offers a potential strategy for managing chemoresistance in CRC.

Chlorogenic Acid Ameliorates Lead-Induced Renal Damage in Mice.

Lead (Pb) exposure is a global environmental problem and its exposure can lead to serious renal damage by disturbing the pro-oxidant/antioxidant balance and facilitating inflammation. Chlorogenic acid (CGA) is one of the most abundant polyphenols in the diet and has been reported to have many biological properties such as antioxidant and anti-inflammatory. In this study, we aimed to investigate the protective efficacy and mechanism of CGA against Pb-induced nephrotoxicity in mice. The results showed that CGA inhibited Pb-induced bodyweight loss, reduced kidney coefficients, and alleviated renal function and structure. Exploration on the potential mechanism demonstrated that CGA suppressed Pb-induced inflammation in the kidney by regulating NF-κB pathway activation. Furthermore, CGA significantly increased Pb-induced reduction in the activity of SOD and GSH-Px, and reduced Pb-induced increase in the content of MDA. The expression of Bax and Bcl-2 associated with apoptosis was also significantly regulated by CGA. These data indicated that CGA may play a potential treatment strategy for Pb toxicity.