Khriesha Abeer, Bustanji Yasser, Abu Farha Rana, Al-Abbasi Reem, Abu-Irmaileh Bashaer
Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, Amman, Jordan.
Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan.
Horm Mol Biol Clin Investig. 2021 Feb 1;42(1):3-9. doi: 10.1515/hmbci-2020-0045.
Vitamin D is very important for calcium and mineral metabolism, and many hypotheses appear to link sunlight exposure with cancer risk and prognosis. As many studies supported the antitumor effect of vitamin D we wanted to investigate the potential effect of multiple vitamin D metabolites.
This study compared the anticancer effect of three inactive forms of vitamin D which are; cholecalciferol, alfacalcidol, and calcifediol on two human cancer cell lines colorectal cancer (CaCo II) and breast cancer (MCF-7). All were examined after 24, 48, and 72 h continuous exposure using a colorimetric assay (MTT) seeded in 96-multiwell plates. Doxorubicin anticancer used as a standard agent for comparison, while normal skin fibroblast cells (HDFa) was used as our negative control. IC values were calculated as indication of antitumor effect.
Broad-spectrum of cytotoxicity with IC values ranging from 4 to 200 μM were found. Alfacalcidol was the most potent cytotoxic agents on colorectal cancer (CaCo II) and breast cancer (MCF-7) compared to cholecalciferol, and calcifediol. Both, alfacalcidol and calcifediol were more cytotoxic than cholecalciferol on the tested cell lines as they are partially active metabolites. Breast cancer (MCF-7) was the most sensitive to all metabolites at all-time intervals with the best IC values of 4.35 μM ± 1.06 after 72 h continuous exposure of alfacalcidol.
Vitamin D metabolites are a potential option for cancer treatment along with or an alternative to chemo-therapeutics although extensive preclinical studies are required to prove this effect.
维生素D对钙和矿物质代谢非常重要，许多假说似乎将阳光照射与癌症风险及预后联系起来。由于许多研究支持维生素D的抗肿瘤作用，我们想要研究多种维生素D代谢物的潜在作用。
本研究比较了三种无活性形式的维生素D，即胆钙化醇、阿法骨化醇和骨化二醇对两种人类癌细胞系结肠直肠癌（CaCo II）和乳腺癌（MCF-7）的抗癌作用。在接种于96孔板中连续暴露24、48和72小时后，使用比色法（MTT）对所有细胞进行检测。多柔比星用作抗癌标准对照剂，而正常皮肤成纤维细胞（HDFa）用作阴性对照。计算IC值以表明抗肿瘤作用。
发现了广谱细胞毒性，IC值范围为4至200μM。与胆钙化醇和骨化二醇相比，阿法骨化醇对结肠直肠癌（CaCo II）和乳腺癌（MCF-7）是最有效的细胞毒性剂。阿法骨化醇和骨化二醇作为部分活性代谢物，在测试细胞系上比胆钙化醇更具细胞毒性。乳腺癌（MCF-7）在所有时间间隔对所有代谢物最敏感，在连续暴露阿法骨化醇72小时后，最佳IC值为4.35μM±1.06。
维生素D代谢物是癌症治疗的一种潜在选择，可与化疗药物联合使用或作为替代方案，尽管需要广泛的临床前研究来证实这种效果。
