Two Worlds Colliding: The Interplay Between Natural Compounds and Non-Coding Transcripts in Cancer Therapy

Abstract

Cancer is a devastating disease and has recently become the leading cause of death in western countries, representing an immense public health burden. When it comes to cancer treatment, chemotherapy is one of the main pillars, especially for advanced stage tumors. Over the years, natural compounds have emerged as one of the most valuable resources for new chemotherapies. It is estimated that more than half of the currently used chemotherapeutic agents are derived from natural compounds. Usually, natural compounds are discovered empirically and an important limitation of introducing new anti-cancer natural products is lack of knowledge with regard to their mechanism of action. Recent data has proven that several natural compounds may function via modulating the expression and function of non-coding RNAs (ncRNAs). NcRNAs are a heterogenous class of RNA molecules which are usually not translated into proteins but have an important role in gene expression regulation and are involved in multiple tumorigenic processes, including response/resistance to pharmacotherapy. In this review, we will discuss how natural compounds function via ncRNAs while summarizing the available data regarding their effects on over 15 types of cancer. Moreover, we will critically analyze the current advances and limitations in understanding the way natural compounds exert these health-promoting effects by acting on ncRNAs. Finally, we will propose several hypotheses that may open new avenues and perspectives regarding the interaction between natural compounds and ncRNAs, which could lead to improved natural compound-based therapeutic strategies in cancer.

Lemongrass Essential Oil Components with Antimicrobial and Anticancer Activities

“…Various classes of bioactives were shown to exert anticancer effects through the downregulation of microRNAs, most often oncomiRs, and the release of mRNAs coding for antiproliferative proteins. The review by Sabo [ 152 ] and that by Cherng [ 153 ] showed the relationship between natural compounds and nc-RNAs in cancer cells, and the potential use of their bioactives in cancer therapies. Xu and colleagues described, for the first time, the involvement of pinene, one component of LEO, in the upregulation of p27/CDKN1B, a cell cycle-blocking protein, through the downregulation of miR-221 [ 153 ].…”

Disease-Associated Regulation of Non-Coding RNAs by Resveratrol: Molecular Insights and Therapeutic Applications

“…Emerging evidence, mainly in the context of cancer research, suggests that the expression of ncRNAs, as well as their downstream targets, can be modulated by the intake of specific nutrients and natural compounds ( Ferrero et al, 2021 ; Scoditti et al, 2021 ). For instance, natural products such as curcumin, resveratrol, and epigallocatechin-3-gallate, have been shown to exhibit anti-cancer effects by modulating the expression and the function of several ncRNAs, with consequent inhibition of cancer cell growth, induction of apoptosis, and increased therapeutic efficacy of conventional cancer therapy ( Zhang B. et al, 2020 ; Sabo et al, 2021 ). Within the above mentioned natural compounds, resveratrol (3, 5, 4′-trihydroxystilbene), a nonflavonoid polyphenol contained in various foods, e.g., grapes, apples, blueberries, cocoa and peanuts, has been extensively studied in view of its numerous biological effects ( Galiniak et al, 2019 ).…”

Curcumin Targeting Non-Coding RNAs in Colorectal Cancer: Therapeutic and Biomarker Implications

“…Indeed, many studies have demonstrated that the development pathogenesis of colorectal cancer is highly influenced by ncRNAs [ 10 ], the abnormal expression of oncogenic and tumor-suppressor molecules, and the abnormal activation of various cell signaling pathways [ 11 , 12 ]. In recent years, some important natural compounds, such as phenolics, terpenoids, and meroterpenoids, have been confirmed to have anticancer effects by regulating the expression and function of ncRNAs [ 13 ]. Particularly, naturally derived polyphenols have been safely used for many years and have shown real potential for therapeutic effects in most cancers through the regulation of miRNAs and lncRNAs [ 14 , 15 , 16 ].…”