Abstract
Naturally occurring dietary agents present in a wide variety of plant products, are rich sources of phytochemicals possessing medicinal properties, and thus, have been used in folk medicine for ages to treat various ailments. The beneficial effects of such dietary components are frequently attributed to their anti-inflammatory and antioxidant properties, particularly in regards to their antineoplastic activities. As many tumor types exhibit greater oxidative stress levels that are implicated in favoring autonomous cell growth activation, most chemotherapeutic agents can also enhance tumoral oxidative stress levels in part via generating reactive oxygen species (ROS). While ROS-mediated imbalance of the cellular redox potential can provide novel drug targets, as a consequence, this ROS-mediated excessive damage to cellular functions, including oncogenic mutagenesis, has also been implicated in inducing chemoresistance. This remains one of the major challenges in the treatment and management of human malignancies. Antioxidant-enriched natural compounds offer one of the promising approaches in mitigating some of the underlying mechanisms involved in tumorigenesis and metastasis, and therefore, have been extensively explored in cancer chemoprevention. Among various groups of dietary phytochemicals, polyphenols have been extensively explored for their underlying chemopreventive mechanisms in other cancer models. Thus, the current review highlights the significance and mechanisms of some of the highly studied polyphenolic compounds, with greater emphasis on pancreatic cancer chemoprevention.
Highlights
Natural dietary polyphenolic compounds are widely distributed in various plant sources and have been explored against several health-related ailments and their associated symptoms, due to their medicinal properties [1,2,3,4,5,6]
These findings suggested that quercetin due to its ability to target a wide array of signaling pathways could be used as a promising combination approach to enhance the efficacy of chemotherapy agents against pancreatic cancer
The PANC-1 cell line exhibited greater apigenin cytotoxicity compared to the PaCa44 cell line, which was dependent on increased induction of intracellular reactive oxygen species (ROS)/decreased antioxidant defenses, mutant p53 reduction, as well as inhibition of mammalian target of rapamycin (mTOR) and heat shock protein 90 (HSP90) [125]. These findings suggested that an interplay between mTOR-HSP90-mut p53-p62-NRF2 mediates apigenin chemoresistance in p53 mutated pancreatic cancer
Summary
Natural dietary polyphenolic compounds are widely distributed in various plant sources and have been explored against several health-related ailments and their associated symptoms, due to their medicinal properties [1,2,3,4,5,6]. Other reports have documented contrasting or inconsistent evidence for polyphenols intake against cardiovascular diseases and cancer [17,18,19,20]. This indicates the need for conducting further randomized controlled trials and observational or behavioral studies in human subjects with such disease conditions [17,18,19,20]. Most chemotherapeutic drugs are not considered good treatment options as a single agent for advanced-stage/metastatic cancers. Given that the underlying chemopreventive mechanisms of polyphenolic compounds have been reviewed in other cancer models, the current review highlights the significance of some of the highly explored polyphenols in pancreatic cancer chemoprevention
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