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Novel Tocopherol Succinate-Polyoxomolybdate Bioconjugate As Potential Anti-Cancer Agent Publisher



Hosseini MS1 ; Haghjooy Javanmard S2 ; Dana N2 ; Rafiee L2 ; Rostami M3
Authors
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Authors Affiliations
  1. 1. Student Research Committee, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Pharmaceutical Sciences Research Center and Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Journal of Inorganic and Organometallic Polymers and Materials Published:2021


Abstract

Despite the promising anti-cancer properties of the polyoxometalates (POMs) compound, they have not yet been reported for clinical use due to their general toxicity. This study reports the synthesis of tocopherol succinate (TS)-polyoxomolybdate (POMo) conjugate (T2POMo) as a novel organic–inorganic hybrid conjugate of POMo and evaluating its anti-cancer properties in vitro. The aim was to introduce a more potent derivative with less general toxicity than initial POMo to cancer treatment studies. The T2POMo conjugate was synthesized using amide bond formation between POMo and TS based on the carbodiimide strategy. The chemical structure of T2POMo conjugate was fully investigated and confirmed using spectroscopy and elemental analysis techniques. The anti-cancer properties of T2POMo conjugate were evaluated on Brest (MCF-7) and prostate cancer (LNCAP) cell lines carefully by the MTT protocol, and the general toxicity was studied on human umbilical vein endothelial cells (HUVEC) similarly. Finally, the quantity of induced apoptosis was carefully evaluated using the flow cytometry technique for the T2POMo conjugate compared to POMo. The cytotoxicity studies showed that tocopherol succinate conjugation altered and regulated the activity and seems to induce great synergistic cytotoxic effects on cancerous cell lines. The half-maximal inhibitory concentration (IC50) on the MCF-7 cell line was about 167.3 μg/mL, and on the LNCAP cell line was about 234.1 μg/mL. The cytotoxicity of T2POMo was significantly greater than that of POMo, and the toxic effects on normal cells were significantly reduced. Flow cytometry results showed that the hybrid conjugate could produce about 61% of apoptosis in the MCF-7 cell line than POMo (36%) alone. Therefore, tocopherol succinate hybrid conjugate (T2POMo) can be introduced as a promising potent anti-cancer agent to further pre-clinical studies. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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