Modulation of long non-coding RNAs by different classes of secondary metabolites from plants : a mini-review on antitumor effects.

Abstract

The broad pharmacological spectrum of plants is related to their secondary metabolism, which is responsible for the synthesis of different compounds that have multiple effects on cellular physiology. Among the biological effects presented by phytochemicals, their use for the prevention

and treatment of cancer can be highlighted. This occurs due to several mechanisms of antitumor ac- tion demonstrated by these compounds, including regulation of the cell signaling pathways and inhibi- tion of tumor growth. In this way, long non-coding RNAs (lncRNAs) appear to be promising targets

for the treatment of cancer. Their deregulation has already been related to a variety of clinical- pathological parameters. However, the effects of secondary metabolites on lncRNAs are still restrict- ed. For this reason, the present review aimed to gather data on phytochemicals with action on

lncRNAs in order to confirm their possible antitumor potential. According to the literature, terpenoid and flavonoid are the main examples of secondary metabolites involved with lncRNAs activity. In addition, the lncRNAs H19, CASC2, HOTAIR, NKILA, CCAT1, MALAT1, AFAP1-AS1, MEG3, and CDKN2B-AS1 can be highlighted as important targets in the search for new anti-tumor agents since they act as modulating pathways related to cell proliferation, cell cycle, apoptosis, cell migration and invasion. Finally, challenges for the use of natural products as a commercial drug were also discussed. The low yield, selectivity index and undesirable pharmacokinetic parameters were emphasized as a

difficulty for obtaining these compounds on a large scale and for improving the potency of its biologi- cal effect. However, the synthesis and/or development of formulations were suggested as a possible

approach to solve these problems. All of these data together confirm the potential of secondary me- tabolites as a source of new anti-tumor agents acting on lncRNAs.