Resveratrol and quercetin alone are well reported to have anticancer potential, but their combination studies are very inadequate. We have examined their combination in Cal-33 and SCC-15 oral cancer cells (OCCs) and noncancerous HEK-293 cells. Combination of 10 μM concentration of each resveratrol and quercetin brought additive effect on cellular growth, DNA damage, S-phase cell cycle arrest, and cell death in Cal-33 cells but not in the HEK-293 cells. Augmentation of the cell cycle regulatory protein, Cyclin E, and downregulation of Cyclin A possibly caused S-phase arrest in Cal-33 cancer cells. Comet formation and presence of gamma-H2AX foci confirmed DNA damage, and cleavage of PARP1 and upregulation in Bax level specified apoptosis after combined treatment. Ratio of transcription activation and repression histone marks was found increased after alone as well as combined treatment. Histone deacetylase (HDAC)1, HDAC3, and HDAC8 were downregulated by resveratrol alone and combined treatment. Conclusively, combination of resveratrol and quercetin brings cell growth inhibition, DNA damage, and cell cycle arrest in OCCs but not in normal cells. Additionally, combined treatment causes downregulation of HDACs and apoptosis in cancer cells and it could be an incisive strategy against oral cancer.

中文翻译：

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白藜芦醇和槲皮素的组合会导致口腔癌细胞的细胞生长抑制，DNA损伤，细胞周期阻滞和凋亡。

据报道，仅白藜芦醇和槲皮素具有抗癌潜力，但它们的联合研究非常不足。我们已经检查了它们在Cal-33和SCC-15口腔癌细胞（OCC）和非癌性HEK-293细胞中的组合。每种白藜芦醇和槲皮素的浓度为10μM的组合，对Cal-33细胞（而非HEK-293细胞）的细胞生长，DNA损伤，S期细胞周期阻滞和细胞死亡产生累加效应。细胞周期调节蛋白Cyclin E的增强和Cyclin A的下调可能导致Cal-33癌细胞的S期停滞。彗星的形成和γ-H2AX灶的存在证实了DNA损伤，联合治疗后PARP1的裂解和Bax水平的上调表明细胞凋亡。单独或联合处理后，发现转录激活和抑制组蛋白标记的比率增加。组蛋白脱乙酰基酶（HDAC）1，HDAC3和HDAC8被白藜芦醇单独和联合处理下调。结论是，白藜芦醇和槲皮素的组合在OCC中可抑制细胞生长，DNA损伤和细胞周期停滞，而在正常细胞中则不会。此外，联合治疗会导致HDAC的下调和癌细胞的凋亡，这可能是针对口腔癌的一种重要策略。