Abstract
The incidence of gastrointestinal cancers is increasing every year. Irinotecan (CPT-11), a drug used in the treatment of colorectal cancer and gastric cancer, is metabolized by carboxylesterases to an active metabolite, SN-38, which is more cytotoxic. CAPE (caffeic acid phenethyl ester) is an active component of propolis, which has a high antibacterial, antiviral, and antineoplastic potential. This study analyses the impact of CAPE on the cytotoxic (MTT assay), genotoxic (comet assay) and proapoptotic (caspase-3/7 activity) potential of irinotecan and its metabolite SN-38 in cultures of gastrointestinal neoplastic cells (HCT116, HT29, AGS). Cytotoxicity and genotoxicity activities of these compounds were carried out in comparison with human peripheral blood lymphocytes (PBLs) in vitro. The antioxidant potential of CAPE was investigated in relation H2O2-induced oxidative stress in the both neoplastic cells and PBLs. CAPE expressed cytotoxic, genotoxic, and pro-apoptotic activity against AGS, HCT116, and HT29 tumor cells. CAPE, in the presence of different concentrations of irinotecan or SN38, decreased the cytotoxicity, genotoxicity, and pro-apoptotic activity in these cell lines, but it has no such action on normal human peripheral blood lymphocytes.
Highlights
Gastric and colorectal cancers are the third and fourth cause of death worldwide and concern~1.5 million people
The cytotoxicity was assessed by means of a MTT test and evaluated by IC50 values, concentration of drug that cause 50% growth inhibition
Our research has shown that caffeic acid phenethyl (CAPE) caused a statistically significant reduction in the level of ROS in cancer cells even compared to the negative control, this may be the reason for the antagonistic effect of CAPE in relation to the observed cytotoxic and genotoxic activity of CPT-11 and SN38
Summary
Gastric and colorectal cancers are the third and fourth cause of death worldwide and concern~1.5 million people. Gastric and colorectal cancers are the third and fourth cause of death worldwide and concern. Irinotecan (CPT-11), a semi-synthetic derivative of the naturally occurring alkaloid camptothecin, is a medication commonly used in the management of gastrointestinal cancers [1]. The cytotoxic effects of CPT-11 and SN38 are time-dependent and specific for the S-phase of the cell cycle [4]. A growing number of neoplastic patients take dietary supplements to minimize the side effects of chemotherapeutic agents, and thereby facilitate the therapeutic effect. Supplementing the everyday diet with vitamins or other exogenous substances is aimed at improving the efficacy of chemotherapy, which does not always have the desired therapeutic effect. There are two contradictory hypotheses concerning the presence of antioxidant dietary supplements taken by patients in the course of Molecules 2020, 25, 658; doi:10.3390/molecules25030658 www.mdpi.com/journal/molecules
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