Melanoma is a notoriously radioresistant type of skin cancer. Elucidation of the specific mechanisms underlying radioresistance is necessary to improve the clinical efficacy of radiation therapy. To identify the key factors contributing to radioresistance, five melanoma cell lines were selected for study and genes that were upregulated in relatively radioresistant melanomas compared with radiosensitive melanoma cells determined via RNA sequencing technology. In particular, we focused on cyclin D1 (CCND1), a well known cell cycle regulatory molecule. In radiosensitive melanoma, overexpression of cyclin D1 reduced apoptosis. In radioresistant melanoma cell lines, suppression of cyclin D1 with a specific inhibitor or siRNA increased apoptosis and decreased cell proliferation in 2D and 3D spheroid cultures. In addition, we observed increased expression of γ‐H2AX, a molecular marker of DNA damage, even at a later time after γ‐irradiation, under conditions of inhibition of cyclin D1, with a response pattern similar to that of radiosensitive SK‐Mel5. In the same context, expression and nuclear foci formation of RAD51, a key enzyme for homologous recombination (HR), were reduced upon inhibition of cyclin D1. Downregulation of RAD51 also reduced cell survival to irradiation. Overall, suppression of cyclin D1 expression or function led to reduced radiation‐induced DNA damage response (DDR) and triggered cell death. Our collective findings indicate that the presence of increased cyclin D1 potentially contributes to the development of radioresistance through effects on RAD51 in melanoma and could therefore serve as a therapeutic target for improving the efficacy of radiation therapy.
Dyglomera ® is an aqueous ethanol extract derived from the fruit and pods of Dichrostachys glomerata. A previous study has revealed that Dyglomera regulates adipogenesis and lipolysis by modulating AMP-activated protein kinase (AMPK) phosphorylation and increased expression levels of lipolysisrelated proteins in white adipose tissue of high fat diet-induced mice and 3T3-L1 adipocyte cells. To further investigate mechanisms of Dyglomera, additional studies were performed using 3T3-L1 cells. Results revealed that Dyglomera downregulated adipogenesis by inhibiting the protein kinase B/mammalian target of rapamycin signaling pathway and reconfirmed that it downregulated gene expression levels of proliferator-activated receptor (PPAR)-γ, CCAAT enhancer binding protein α, sterol-regulation elementbinding protein-1c. Dyglomera also reduced adipokines such as tumor necrosis factor alpha, interleukin-1β, and interleukin 6 by regulating leptin expression. Moreover, Dyglomera promoted beige-and-brown adipocyte-related phenotypes and regulated metabolism by increasing mitochondrial number and expression levels of genes such as T-box protein 1, transmembrane protein 26, PR domain 16, and cluster of differentiation 40 as well as thermogenic factors such as uncoupling protein 1, proliferatoractivated receptor-gamma co-activator-1α, Sirtuin 1, and PPARα through AMPK activation. Thus, Dyglomera not only can inhibit adipogenesis, but also can promote lipolysis and thermogenesis and regulate metabolism by affecting adipokine secretion from 3T3-L1 adipocytes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.