da Costa Araldi Isabel Cristina, Bordin Fernando Primitivo Romero, Cadoná Francine Carla, Barbisan Fernanda, Azzolin Verônica Farina, Teixeira Cibele Ferreira, Baumhardt Tadeu, da Cruz Ivana Beatrice Mânica, Duarte Marta Maria Medeiros Frescura, Bauermann Liliane de Freitas
Laboratory of Experimental Physiology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Laboratory of Biogenomics, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Chem Biol Interact. 2018 Feb 25;282:85-92. doi: 10.1016/j.cbi.2018.01.013. Epub 2018 Jan 12.
Radiation therapy is commonly applied in breast cancer (BC) patients. However, radioresistance and side effects are limiting factors of this practice. Therefore, studying substances that can enhance the radiation effect and, at the same time, protect normal cells is very relevant. Thus, the aim of this work was to assess the radiosensitizer effect of resveratrol (RV) on BC cells (MCF-7). A high cytotoxic and antiproliferative effect was observed in the treatment with 10 μM of RV + 3 Gy ionizing radiation (IR). Our results indicate that, 24 h after the exposition of cell cultures to RV + IR, an induction of necrosis/senescence has occurred. Furthermore, was observed the activation of extrinsic apoptosis pathway through a decrease of the Bax/Bcl-2 ratio and a high activity of caspase 8. Moreover, our data show that this treatment affected the oxidative cell metabolism, increasing oxidative protein, lipid and membrane damage and also acted to decrease the antioxidant enzymes activity. The antiproliferative effect on 72 h cultures may be associated with a high expression of p53 and an interruption of cell cycle in the S phase. Therefore, our results suggest that RV is a potential radiosensitizer of MCF-7 BC cells.
放射治疗常用于乳腺癌（BC）患者。然而，放射抗性和副作用是这种治疗方法的限制因素。因此，研究能够增强放射效果且同时保护正常细胞的物质具有重要意义。因此，本研究的目的是评估白藜芦醇（RV）对BC细胞（MCF-7）的放射增敏作用。在用10 μM的RV + 3 Gy电离辐射（IR）处理时观察到了高细胞毒性和抗增殖作用。我们的结果表明，细胞培养物暴露于RV + IR后24小时，发生了坏死/衰老诱导。此外，通过Bax/Bcl-2比值的降低和caspase 8的高活性观察到了外源性凋亡途径的激活。此外，我们的数据表明，这种处理影响了细胞的氧化代谢，增加了氧化蛋白质、脂质和膜损伤，并且还起到降低抗氧化酶活性的作用。对72小时培养物的抗增殖作用可能与p53的高表达以及S期细胞周期的中断有关。因此，我们的结果表明RV是MCF-7 BC细胞的潜在放射增敏剂。
