Objectives: Anthracycline drugs such as Doxorubicin are considered one of the most active, wide-spectrum, and cost-effective drugs that have been used as a therapy for many cancers, but not for colorectal cancer. Recent reports indicate that inhibiting Aldose Reductase increases the sensitivity of human colorectal cancer cells to Doxorubicin. In the present study, we have investigated the effect of using an Aldose Reductase inhibitor (Fidarestat) as an adjuvant drug with Doxorubicin on

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... l cell line Caco-2, by studying cell viability, type of death, and cell cycle distribution in order to understand the pathways of this treatment. Results: Our results indicated that Fidarestat significantly increased the sensitivity of Caco-2 cells to Doxorubicin in a concentration-independent manner. In addition, Fidarestat increased Doxorubicin-induced G2/M phase arrest as well as induced cell cycle arrest in the S phase, thus potentiated Doxorubicin cytotoxicity. over all, our results demonstrated that a potent and clinically safe Aldose Reductase inhibitor, Fidarestat, sensitized Caco-2 cells to Doxorubicin via increasing Doxorubicin cell cycle-dependent cytotoxicity.