Antioxidants Acteoside and Orientin as Emerging Agents in Synergistic Cancer Therapy: A Focus on Innovative Applications.

Cancers, particularly those resistant to treatment, stand as one of the most significant challenges in medicine. Frequently, available therapies need to be improved, underscoring the necessity for innovative treatment modalities. Over the years, there has been a resurgence of interest in natural plant substances, which have been traditionally overlooked as anticancer agents. A prime example of this is natural antioxidants, such as acteoside (ACT) and orientin (ORI), which offer novel approaches to cancer treatment, emphasizing liver cancer compared to other cancer types. They reduce oxidative stress by activating the Nrf2/ARE pathway and exhibit anticancer activity, e.g., decreasing Bcl-2 and Bcl-XL expression and increasing Bax levels. This review explores the individual effects of ACT and ORI and their synergistic interactions with sorafenib, temozolomide, 5-fluorouracil (for ACT), celecoxib, and curcumin (for ORI), highlighting their enhanced anticancer efficacy. In addition, ACT and ORI successfully integrate into various drug delivery systems (DDSs), including metal-containing carriers such as nanoparticles (NPs), nanoshells (NSs), quantum dots (QDs), and liposomes as representative examples of lipid-based drug delivery systems (LBDDSs). Advanced methods, including nanotechnology, offer potential solutions to low bioavailability, paving the way for the use of these substances in anticancer therapy.