Support needs for chronic disease self-management among persons attending a Primary Health Care facility in Victor Khanye, Mpumalanga.

Cervical cancer remains one of the leading causes of cancer-related incidence and mortality among women worldwide. According to GLOBOCAN 2022 estimates, ~662,000 new cases of cervical cancer and 349,000 associated deaths were reported globally in 2022 (). Early-stage cervical cancer is usually treated with conization; however, when early detection fails and metastasis occurs, patients require treatment with chemotherapy, with alkylating agents and antitumor antibiotics commonly used (). However, various challenges, including the high toxicity of anticancer drugs and the relatively high cost of treatment, indicate that further research to improve anticancer treatment strategies is still required (). Cervical cancer, which is primarily caused by a persistent infection with a high-risk strain of the human papillomavirus (HPV), is characterized by HPV-mediated alterations to, and functional inactivation of, tumor suppressor proteins, including p53. Accordingly, strategies aimed at restoring the activity and expression of tumor suppressor proteins may represent a promising therapeutic approach for cervical cancer (). Notably, studies have demonstrated that phytochemicals can modulate the expression of tumor suppressor proteins in cancer cells (,); thus highlighting the need to evaluate the therapeutic potential of phytochemicals in the treatment of cervical cancer. Phytochemicals are naturally occurring plant-derived compounds that exhibit relatively low biological toxicity compared with synthetic drugs (). Because of these benefits, phytochemicals are being explored for the treatment of various diseases, including cancer and Alzheimer's disease (,). Phytochemicals are broadly classified into polyphenols, terpenoids, alkaloids and organosulfur compounds, each with distinct chemical structures and biological activities. Among these, polyphenols have attracted considerable attention due to their potent antioxidant and anticancer properties, and include subclasses such as flavonoids and phenolic acids (). Flavonoids are a major class of polyphenols with a C6-C3-C6 structure and include subclasses such as flavones, flavanols, flavanones and isoflavones (). Previous studies have reported that flavonoids exhibit antioxidant and anticancer properties in various cancer types, including breast, colorectal, lung and liver cancer, and are generally associated with low toxicity toward normal cells (,). However, a number of flavonoids have limited bioavailability and polymethoxylated flavonoids (PMFs) have emerged as a promising strategy to address this limitation (,). Tangeretin (TAN) is a PMF found predominantly in citrus peels. It has been suggested that the multiple methoxy (−OCH) groups of TAN may contribute to its enhanced chemical stability and resistance to oxidative degradation compared with other flavonoids (). According to a previous pharmacokinetic study, TAN exhibits higher bioavailability than other PMFs, including nobiletin and sinensetin, thus suggesting that TAN may possess relatively favorable pharmacokinetic properties compared with other PMFs (). These pharmacokinetic characteristics could contribute to the biological activity of TAN in cellular systems. TAN has been reported to exert anticancer effects associated with increased intracellular reactive oxygen species (ROS) levels, apoptosis and cell cycle arrest; these effects have been observed in multiple cancer types, including lung, colon and gastric cancer (–). However, to the best of our knowledge, the anticancer effects of TAN on cervical cancer have not yet been elucidated, highlighting the need for further investigation. The present study aimed to evaluate the effects of TAN on cervical cancer cell viability, proliferation and migration. Furthermore, the ability of TAN to induce mitochondrial ROS generation and apoptosis was investigated, and changes in p53 protein expression following TAN treatment were examined.