<p>Isovitexin Suppresses Cancer Stemness Property And Induces Apoptosis Of Osteosarcoma Cells By Disruption Of The DNMT1/miR-34a/Bcl-2 Axis</p>

Abstract

BackgroundIsovitexin (apigenin-6-C-glucoside, ISOV) is a natural flavonoid that exhibits tumor suppressive activity on various types of cancer. However, it is unknown whether the mechanism of its action in osteosarcoma (OS) is associated with epigenetic regulation and whether it involves DNA methyltransferase 1 (DNMT1), microRNAs and their targets.Materials and methodsThe present study investigated the effects of ISOV on DNMT1 activation and miR-34a and Bcl-2 expression levels in order to explain the mechanism underlying ISOV-mediated repression of proliferation and stemness. In addition, the induction of apoptosis in the spheres derived from OS cells was investigated.ResultsThe results indicated that ISOV significantly repressed survival, induced apoptosis and decreased the level of CD133, CD44, ABCG2 and ALDH1 mRNA in the spheres derived from U2OS (U2OS-SC) and MG63 cells (MG63-SC). ISOV further reduced the sphere formation rate of U2OS-SC and MG63-SC. It is important to noted that, ISOV inhibited tumor growth and reduced tumor size of U2OS-SC xenografts in nude mice, which was accompanied by decreased CD133 protein levels, elevated apoptotic index, downregulation of proliferating cell nuclear antigen (PCNA) expression, reduced DNMT1 activity and expression, increased miR-34a and decreased Bcl-2 levels. We identified that Bcl-2 as a direct functional target of miR-34a. Furthermore, ISOV exhibited a synergistic effect with 5-aza-2′-deoxycytidine, the miR-34a mimic or ABT-263 in order to repress cell survival, induce apoptosis, downregulate CD133, CD44, ABCG2 and ALDH1 mRNA expression levels and reduce sphere formation rates of U2OS-SC and MG63-SC cells.ConclusionThe findings suggested that ISOV-mediated epigenetic regulation involved the DNMT1/miR-34a/Bcl-2 axis and caused the suppression of stemness and induction of apoptosis in the spheres derived from OS cells. The data indicated that ISOV exhibited a novel efficient potential for the treatment of OS.

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…In the osteosarcoma model, isovitexin further induced apoptosis and caused epigenetic regulation through the DNA methyltransferase 1 (DNMT1)/miR-34a/Bcl-2 axis, causing the suppression of stemness and inducing apoptosis in the spheres derived from osteosarcoma cells. Isovitexin also decreased tumor growth and size in a murine xenograft model [401]. In liver cancer, isovitexin decreased sphere and colony formation rates and stemness-associated markers by downregulating FoxM1 via inhibition of MnSOD.…”

“…When combined with doxorubicin and sorafenib, vitexin had apoptotic effects [405]. Isovitexin had antiproliferative effects in prostate cancer cells and osteosarcoma cells [400,401]. In the osteosarcoma model, isovitexin further induced apoptosis and caused epigenetic regulation through the DNA methyltransferase 1 (DNMT1)/miR-34a/Bcl-2 axis, causing the suppression of stemness and inducing apoptosis in the spheres derived from osteosarcoma cells.…”

Detection of flavone C-glycosides in the extracts from the bark of Prunus avium L. and Prunus cerasus L.

“…For example vitexin or isovitexin show a number pharmacological properties, however, the most promising seems to be their anticancer activity. [7][8][9][10] Vicenin-2 is known to show hepaprotective, anticancer and antiinflammatory activities. [11][12][13][14] A large variety of Prunus species, e.g.…”

Isovitexin Depresses Osteoarthritis Progression via the Nrf2/NF-κB Pathway: An in vitro Study

“…Multiple studies have demonstrated protective effects of IVX on inflammatory-related diseases like Alzheimer’s disease, 36 neuroinflammation, 37 osteosarcoma, 38 and liver cancer. 39 To test IVX-induced protection of OA, isolated chondrocytes were exposed to a range of working and non-toxic IVX concentrations.…”