期刊
JOURNAL OF INORGANIC AND ORGANOMETALLIC POLYMERS AND MATERIALS
卷 31, 期 7, 页码 3183-3195出版社
SPRINGER
DOI: 10.1007/s10904-021-01998-z
关键词
Anderson type polyoxomolybdate (POMo); Hybrid organic– inorganic bioconjugate; Tocopherol succinate (TS); Apoptosis; Anti-cancer agent
资金
- Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences [297079]
This study synthesized the T2POMo conjugate as a novel organic-inorganic hybrid compound, with the goal of introducing a more potent derivative with less general toxicity than initial POMo for cancer treatment studies. The cytotoxicity of T2POMo was significantly greater than that of POMo on cancer cell lines, while the toxic effects on normal cells were reduced. Flow cytometry results showed that the hybrid conjugate induced more apoptosis in cancer cells compared to POMo alone, suggesting T2POMo as a promising anti-cancer agent for further pre-clinical studies.
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 mu g/mL, and on the LNCAP cell line was about 234.1 mu g/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.
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