Antagonistic Effects of CAPE (a Component of Propolis) on the Cytotoxicity and Genotoxicity of Irinotecan and SN38 in Human Gastrointestinal Cancer Cells In Vitro

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.

Propolis and its potential against SARS-CoV-2 infection mechanisms and COVID-19 disease

“…Japanese scientists have isolated and patented various Brazilian propolis components for cancer treatment [ 66 ], demonstrating their usefulness. In fact, propolis has a wide spectrum of pharmacological properties and is a dietary supplement that is commonly consumed by both healthy and sick people as a preventative precaution and for treatment [ [67] , [68] , [69] ]. It is also used in veterinary medicine, due its antibacterial, antifungal, antiviral, antiparasitic, hepatoprotective, and immunomodulatory activities [ 70 ].…”

Anticancer Activity of Propolis and Its Compounds

“…Quercetin inhibits chemically induced oral carcinogenesis in rats [ 16 ]. Among the ingredients of propolis, CAPE expressed cytotoxic activity against AGS (human adenocarcinoma of the stomach cells), HCT116, and HT29 (colorectal adenocarcinoma) tumor cells [ 38 ].…”

“…It has pro-apoptotic activity through the caspase-3/7 pathway. CAPE significantly increased apoptosis mediated by TRAIL (tumor necrosis factor-related apoptosis ligand inducer) by positive regulation of DR5 (death receptor 5) mediated by CHOP (C/EBP family transcription factor) [ 36 , 38 , 49 , 63 ]. CAPE also affects the apoptotic intrinsic pathway by increasing ROS production and also decreases expression of apoptosis inhibitors such as transporter associated with antigen processing 1 (cTAP-1), baculoviral IAP repeat-containing protein3 (cIAP-2), and X-linked inhibitor of apoptosis protein (XIAP) [ 3 , 63 ].…”

A New Inhibitor of Tubulin Polymerization Kills Multiple Cancer Cell Types and Reveals p21-Mediated Mechanism Determining Cell Death after Mitotic Catastrophe

“…Mice xenografted with HT-29 cells (Figure 2a), and OAT-449 administered intraperitoneally at a dose of 5 mg/kg, daily for 5 days followed by 2 day intervals thereafter, showed a significant antitumor effect compared with the negative control (vehicle, solutol alone, (Sigma-Aldrich, St Louis, MO, USA)). The tumor growth inhibition rate was similar to that observed for irinotecan (CPT-11) employed as the efficient positive control for colorectal cancer cell lines [21]. For the next xenograft experiment, we selected SK-N-MC cells, a human tumor cell line with well-documented sensitivity to vincristine [19].…”