Romanian Society of Pharmaceutical Sciences

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ANTICANCER EFFECTS OF CO-ADMINISTRATION OF DAUNORUBICIN AND RESVERATROL IN MOLT-4, U266 B1 AND RAJI CELL LINES

HMOUD HASHEMZAEI1, SAEED PUDINE KARAMI1, AMIN DELARAMIFAR1, ALIREZA SHEIDARY1, KAVEH TABRIZIAN1,2, RAMIN REZAEE3, SHABNAM SHAHSAVAND3, ANDREEA LETIȚIA ARSENE4, ARISTIDIS MICHAEL TSATSAKIS5, SEYED MOHAMMAD TAGHDISI6*

1.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
2.Medicinal Plants Research Center, Zabol University of Medical Sciences, Zabol, Iran
3.Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
4.Department of Biochemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, sector 2, Bucharest, Romania
5.Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece
6.Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

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Resveratrol (RES) is a naturally occurring compound with strong anti-oxidant effects that combats cancer via several mechanisms. It has been found to inhibit P-glycoprotein and protect cells from chemotherapeutics adverse effects. Daunorubicin (DAN) is mostly used in the treatment of leukaemia and some solid tumour such as glioma. In the current study, we evaluated the effect of co-administration of RES and DAN (RES/DAN) in MOLT-4, U266 B1 and Raji cell lines. MTT assay was used to investigate cell viability at different concentrations of RES, DAN and RES/DAN. Also, to elucidate the mechanism of cell death, flow cytometry study of Annexin V/PI staining was used. Our results from MTT assay showed that RES and DAN induce cell death. IC50 for RES (20 μM for MOLT-4, 73 μM for U266 B1 and 47 μM for Raji cell lines) and IC50 for DAN (0.5 μM for MOLT-4, 0.5 μM for U266 B1 and 0.6 μM for Raji cell lines) were calculated. Flow cytometry study using Annexin V/Pi showed induction of apoptosis following RES, DAN and RES/DAN. The effects of RES/DAN were significantly more marked as compared to DAN and RES (p < 0.001). Taken together, RES and DAN showed synergistic effects in induction of apoptosis in leukaemia cell lines.