Effects of polyphenols on doxorubicin-induced oral keratinocyte cytotoxicity and anticancer potency against oral cancer cells
Effects of polyphenols on doxorubicin-induced oral keratinocyte cytotoxicity and anticancer potency against oral cancer cells
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DOI：
10.1111/jop.12685
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发表时间：
2018-04-01
影响因子：
3.3
通讯作者：
Tachibana, Katsuro
中科院分区：
文献类型：
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作者：
Sheng, Hong;Ogawa, Toru;Tachibana, Katsuro
背景正常人口腔角质形成细胞对阿霉素等抗癌药物高度敏感。白藜芦醇、表没食子儿茶素没食子酸酯和鞣酸是多酚类化合物，据报道与阿霉素联合使用时具有心脏保护作用。然而，目前尚不清楚这些多酚是否可以保护正常人口腔角质形成细胞免受阿霉素诱导的细胞毒性，而不削弱其对口腔癌细胞的细胞毒性潜力。在这里，我们研究了3多酚类化合物对阿霉素诱导的细胞毒性在正常人口腔角质形成细胞的影响，并探讨了它们对阿霉素效力HSC-2人口腔鳞状细胞癌cells.MethodsCell活力进行了评价，然后通过分析凋亡和坏死。在治疗后的早期阶段细胞内活性氧的变化也examined.ResultsThe结果显示，白藜芦醇与多柔比星相加增强多柔比星的细胞毒性在这两种类型的细胞。然而，一定浓度的表没食子儿茶素没食子酸酯和鞣酸减轻了阿霉素诱导的角质形成细胞毒性，主要是由于减少了阿霉素诱导的正常人口腔角质形成细胞的坏死，而没有减弱阿霉素的抗癌功效。确切的机制仍然是未知的，但细胞内的活性氧可能不是唯一的factor.ConclusionsThis研究首次报道的影响，白藜芦醇，表没食子儿茶素没食子酸酯，单宁酸对阿霉素诱导的细胞毒性在正常的口腔角质形成细胞和口腔癌细胞。表没食子儿茶素没食子酸酯或鞣酸与阿霉素在一定浓度下联合使用可减轻阿霉素诱导的角质形成细胞毒性而不减弱阿霉素的抗癌功效。
BackgroundNormal human oral keratinocytes are highly sensitive to anticancer drugs including doxorubicin. Resveratrol, epigallocatechin gallate, and tannic acid are polyphenolic compounds that were reported to have cardioprotective effect when combined with doxorubicin. However, it is unknown whether these polyphenols could protect normal human oral keratinocytes against doxorubicin-induced cytotoxicity without weakening its cytotoxic potential against oral cancer cells. Here, we examined the effects of the 3 polyphenolic compounds on doxorubicin-induced cytotoxicity in normal human oral keratinocytes and also investigated their effects on doxorubicin potency in HSC-2 human oral squamous cell carcinoma cells.MethodsCell viability was evaluated, followed by the analysis of apoptosis and necrosis. The changes in intracellular reactive oxygen species at the early stage after treatment were also examined.ResultsThe results revealed that resveratrol in combination with doxorubicin additively augmented doxorubicin cytotoxicity in both types of cells. However, epigallocatechin gallate and tannic acid at a certain concentration mitigated the doxorubicin-induced keratinocyte toxicity mainly due to reduced doxorubicin-induced necrosis in normal human oral keratinocytes without weaken doxorubicin anticancer efficacy. The exact mechanism is still unknown but intracellular reactive oxygen species might be not the sole factor.ConclusionsThis study for the first time reported the effects of resveratrol, epigallocatechin gallate, and tannic acid on doxorubicin-induced cytotoxicity in normal oral keratinocytes and oral cancer cells. The combined use of epigallocatechin gallate or tannic acid with doxorubicin at a certain concentration could mitigate doxorubicin-induced keratinocyte cytotoxicity without weakening doxorubicin anticancer efficacy.