Abstract
Cancer is a global health concern and one of the main causes of disease-related death. Even with considerable progress in investigations on cancer therapy, effective anti-cancer agents and regimens have thus far been insufficient. There has been compelling evidence that natural phytochemicals and their derivatives have potent anti-cancer activities. Plant-based anti-cancer agents, such as etoposide, irinotecan, paclitaxel, and vincristine, are currently being applied in medical treatments for patients with cancer. Further, the efficacy of plenty of phytochemicals has been evaluated to discover a promising candidate for cancer therapy. For developing more effective cancer therapy, it is required to apprehend the molecular mechanism deployed by natural compounds. MicroRNAs (miRNAs) have been realized to play a pivotal role in regulating cellular signaling pathways, affecting the efficacy of therapeutic agents in cancer. This review presents a feature of phytochemicals with anti-cancer activity, focusing mainly on the relationship between phytochemicals and miRNAs, with insights into the role of miRNAs as the mediators and the regulators of anti-cancer effects of phytochemicals.
Highlights
The expression of miR-137 is epigenetically silenced in glioblastoma, and the overexpression of miR-137 blocks the invasion of cancer cells, indicating that miR-137 is a tumor-suppressive miRNA in glioblastoma [282]
Tumor-suppressive miRNAs, such as miR-29-3p, miR-193-3p, and miR-196-5p, have been reported to target anti-apoptotic messenger RNAs (mRNAs) and enhance the cytotoxicity of etoposide, showing the following: miR-29-3p sensitizes cervical cancer cells to etoposide by targeting myeloid cell leukemia sequence 1 (MCL1), a member of the B-cell CLL/Lymphoma 2 (BCL-2) family [293]; miR-193-3p targets insulin receptor substrate 2 (IRS2) and improves the effectiveness of etoposide in osteosarcoma cells [294]; miR-196-5p escalates etoposide-induced apoptosis via inhibiting insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) [295] (Figure 5 and Table 6)
The accumulating evidence presented here indicates that phytochemicals have valuable potentials as therapeutic agents against cancer
Summary
Anti-cancer agents currently used in clinical therapy are derived from plants. This article aims to present a review of the role of miRNAs in mediating and regulating the anti-cancer effects of phytochemicals. (NCT02064673, prostate cancer, recruiting) A flavonoid in fruits and vegetables such as tomatoes. A polyphenol in green tea (NCT02891538, colorectal cancer, recruiting) An isoflavone in the root of Astragalus membranaceus. A sesquiterpene lactone from Artemisia annua A derivative of artemisinin (NCT02633098, colorectal cancer, recruiting) A pentacyclic triterpenoid from Astragali radix A triterpene quassinoid in Brucea javanica fruit A terpenophenolic compound from Cannabis sativa (NCT04428203, prostate cancer, recruiting) A triterpene in Tripterygium wilfordii. A triterpenoid saponin from Bolbostemma paniculatum A pentacyclic triterpene in plants such as apples (NCT04403568, prostate cancer, not yet recruiting) A monoterpene in pine needles [32] [33] [34]. Oncogenic MiRNAs Inhibited by Phytochemicals Currently Evaluated in Preclinical Studies and Clinical Trials
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