Resveratrol enhances the radiosensitivity of nasopharyngeal carcinoma cells by downregulating E2F1

Abstract

Identification of safe, effective radiosensitizing agents is urgently needed to improve the outcome of radiotherapy in nasopharyngeal cancer (NPC). In this study, we assessed the ability of the polyphenol resveratrol to act as a radiosensitizer in vitro and in vivo. CNE-1 cells were treated with 50 µM resveratrol for 24 h, then irradiated. E2F transcription factor 1 (E2F1) was stably knocked down and overexpressed using lentiviruses. A xenograft model of NPC was established in nude mice using CNE-1 cells. Compared to control DMSO‑treated CNE-1 cells, resveratrol inhibited colony-forming ability and induced G1 phase cell cycle arrest. Radiation survival curves confirmed resveratrol significantly sensitized CNE-1 cells, and resveratrol in combination with 2 Gy irradiation synergistically increased apoptosis. Immunoblotting showed resveratrol dose- and time-dependently downregulated E2F1 and phospho-AKT (p-AKT). Knockdown of E2F1 significantly increased radiosensitivity and downregulated p-AKT; overexpression of E2F1 reversed resveratrol-induced radiosensitivity and upregulated p-AKT. In vivo, 50 mg/kg/day resveratrol and 4 Gy irradiation led to significantly lower tumor volume and tumor weight compared to resveratrol or irradiation alone. Our findings show that resveratrol increases the radiosensitivity of NPC cells by downregulating E2F1 and inhibiting p-AKT, and therefore has potential as a radiosensitizer for NPC.

CYP1B1 as a therapeutic target in cardio-oncology

“…When combined with radiation therapy, resveratrol has been shown to augment the anti-cancer effects of radiation in both in vitro and in vivo studies [320][321][322][323][324], as reviewed in [250]. For instance, resveratrol has proven in the past to offer radiosensitizing effects in nasopharyngeal cancer cells via inhibition of E2F transcription factor, colony-forming activities, and the induction of G 1 phase cell cycle arrest [325]. Apigenin has been shown to enhance the apoptotic effects of radiation in SQ-5 human lung carcinoma cells by increasing the protein expression of WAF1/p21 while decreasing protein levels of Bcl-2 [326].…”

Resveratrol Suppresses Human Nasopharyngeal Carcinoma Cell Growth Via Inhibiting Differentiation Antagonizing Non-Protein Coding RNA (DANCR) Expression

“…Resveratrol exerts anticancer effects through mediating the function of molecular targets associated with cell proliferation, cell cycle and apoptosis [ 7 ]. Recently, research has revealed the potent anti-proliferative and pro-apoptotic effects of resveratrol in NPC [ 8 ]. However, the molecular mechanism involved in the effects of resveratrol in NPC is poorly understood.…”

Cancer-testis specific gene OIP5: a downstream gene of E2F1 that promotes tumorigenesis and metastasis in glioblastoma by stabilizing E2F1 signaling

“…18 Aberrant E2F1 upregulation, which is associated with malignant processes and poor prognosis, is frequently observed in many kinds of human cancers. [19][20][21][22] Moreover, E2F1 is also associated with radiosensitivity 23 and chemosensitivity 24,25 in cancer cells. While some findings showing that E2F1 is involved in cell senescence and apoptosis may suggest its dual role in tumor formation, 26 several events accelerating the development of cancer may neutralize the tumor-suppressive functions of E2F1.…”