Cytotoxicity of main anthraquinone aglycons towards drug sensitive and multi drug resistant T leukaemia cancer cells

Cancer as one of the leading causes of mortality is increasing regularly worldwide [1]. Multidrug resistant (MDR) cancer cells constitute a serious problem in chemotherapy. The modulation of resistance-mediated genes or proteins by phytochemicals can be an attractive strategy to overcome MDR resistance in cancer, in regards to the diversity of chemical structures in plant kingdom. Naturally occurring anthranoids as anthracene derivatives are mostly present in Rumex, Rhamnus, Rheum species [2, 3]. Anthraquinones, the major group of naturally occurring quinones are distinguished by a large structural diversity, wide range of biological activity, and low toxicity [4]. They exhibit a wide range of bioactivities such as anticancer as well as antimicrobial, hypotensive, antimalarial, analgesic and anti-inflammatory [4 – 6]. In this study we investigated the cytotoxicity of the four anthraquinones emodin, aloe-emodin, physcion and rhein against drug sensitive leukemia CCRF-CEM cells and their resistance counterpart P-glycoprotein-over-expressing CEM/ADR5000 leukaemia cells. The resazurin reduction assay was used to evaluate the cytotoxicity of the compounds. The recorded IC₅₀ values for compounds were ranged from 11.95µM to 142.44µM towards CCRF-CEM and from 22.41µM to 90.69µM towards CEM/ADR5000 cells. Clinically used anticancer drug doxorubicin had the following IC₅₀ values: 0.0007µM towards CCRF-CEM and 48.9µM towards CEM/ADR5000 cells. Compared to their corresponding sensitive cell lines, collateral sensitivity (hypersensitivity) was observed in drug-resistant P-glycoprotein over-expressing CEM/ADR5000 cells (0.67 fold) to physcion. In conclusion, we demonstrated the cytotoxicity of few main anthraquinone aglycons against drug-sensitive and MDR leukaemia cancer cells. In particular aloe-emodin might be a potential cytotoxic natural agent that deserves more investigations to develop novel antineoplastic drugs.

Acknowledgments: This study was supported by The Scientific and Technological Research Council of Turkey (TÜBITAK) 2214-A scholarship.

Keywords: Anthraquinone, cytotoxicity, Resazurin reduction assay, mutidrug resistant (MDR), cancer.

References:

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