Indeed, the proposed mechanisms of action through which resveratrol exerts its anticancer effects involve multiple pathways. These specific mechanisms have been corroborated in different types of cancer, and recent studies have suggested that resveratrol may also be useful when given in combination with other agents (Singh et al., 2013). In this respect, resveratrol stimulates the apoptosis of tumor cells, prevents tumor-derived nitric oxide synthase expression, blocks tumor growth and migration, and also inhibits the cyclooxygenase (COX) activity (Aggarwal et al., 2004). In a tumor microenvironment, resveratrol has shown to directly interfere with cancer initiation, promotion, and progression (significant stages of carcinogenesis) (Aggarwal et al., 2004 Summerlin et al., 2015 Velmurugan et al., 2018). Illustration showing various components discussed in the current review. With a broad action as an antioxidant (Öztürk et al., 2017), resveratrol has shown excellent chemopreventive and chemotherapeutic effects against certain types of cancers ( Figure 1). Interestingly, resveratrol is a plant secondary metabolite, phytoalexin, produced as a result of the adaptive reaction to environmental stress factors, such as fungal infections, injury, and UV irradiation (Langcake and Pryce, 1976 Bhat et al., 2001a Jeandet et al., 2010 Aluyen et al., 2012 Summerlin et al., 2015). This molecule is a natural stilbenoid with the chemical formula 3,5,4′-trihydroxy-trans-stilbene. Despite its isolation in 1939 firstly from the roots of the Japanese plant Polygonum cuspidatum (Timmers et al., 2012), resveratrol is an important antioxidant present abundantly in red grapes, red wine, and a variety of other dietary sources, such as peanuts, raspberries, blueberries, and mulberries (Chong et al., 2009 Jasiński et al., 2013 Weiskirchen and Weiskirchen, 2016 Jeandet et al., 2021). Among this broad class of compounds, resveratrol has gaining a key scientific interest due its good anticancer and antioxidant effects (Summerlin et al., 2015). However, considering their low stability as a limiting factor, the topical application of nanopolyphenols is thought to represent a valuable technology to overcome some limitations in pharmacokinetics, targeting efficacy, and safety concerns (Menaa et al., 2014). Indeed, the role of polyphenols as oxidative stress modulators in cancer has been deeply discussed (Mileo and Miccadei, ( n.d.)). However, careful attention must be paid in the development of effective targeted formulations that can contribute to raise therapeutic outcomes while exerting no significant damage to the tissues (Revia and Zhang, 2016 Navya et al., 2019).Īmong active natural compounds, polyphenols are gaining high popularity because of their bioavailability traits and promissory beneficial effects, including antioxidant, anti-inflammatory, antiaging, and anticancer properties (Upadhyay and Dixit, 2015 Karakaya et al., 2019). Different nanoformulations have been compared to the already available anticancer drugs among other aspects, they have revealed to be more soluble, stable, effective, and improved biodistribution pattern. In addition, a growing emphasis has been placed on naturally occurring bioactive compounds for chemotherapy and chemoprevention in several kinds of cancer, and secondly, there has been a more pronounced focus on nanotherapy where the proof-of-concept of cancer prevention using nanoformulations is in a stage of rapid development (Navya et al., 2019). Presently, several smart drug delivery systems, such as carbon-based and polymeric materials, metallic nanoparticles, or liposomes, have been adopted for cancer treatment. Molecular targeted therapy has been developed as a promising tool to overcome the lack of specificity of chemotherapeutic agents, and in such a framework, nanotechnology emerges as a powerful strategy (Gu et al., 2009 Sanna et al., 2013a).
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