Abstract
Background
Normal human oral keratinocytes are highly sensitive to anticancer drugs including doxorubicin. Resveratrol, epigallocatechin gallate and tannic acid are polyphenolic compounds 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 three 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.
Methods
Cell 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.
Results
The 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 concentrations 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.
Conclusions
The present 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. Combined use of epigallocatechin gallate or tannic acid with doxorubicin at a certain concentrations could mitigate doxorubicin-induced keratinocyte cytotoxicity without weakening doxorubicin anticancer efficacy.
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