Bursa Uludag University, Faculty of Science and Arts, Department of Biology, 16059 Bursa, Turkey; Istanbul University, Aziz Sancar Experimental Medicine Research Institute, Molecular Medicine, 34093 Istanbul, Turkey.
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrent'ev Ave., 9, 630090 Novosibirsk, Russia.
Bioorg Med Chem. 2021 Jan 15;30:115963. doi: 10.1016/j.bmc.2020.115963. Epub 2020 Dec 29.
Being one of the leading causes of cancer death among women, various chemotherapeutic agents isolated from natural compounds are used in breast cancer treatment and consequently studies to develop new drugs still continue. There are several studies on 18βH-glycyrrhetinic acid, a secondary metabolite which is found in Glycyrrhiza glabra (liquorice roots), as a potential anticancer agent. In this study, the cytotoxic and apoptotic effects of Soloxolone methyl compound, a semisynthetic derivative of 18βH-glycyrrhetinic acid were investigated on breast cancer cells (MCF-7, MDA-MBA-231). Soloxolone methyl is found to be cytotoxic on both MCF-7 and MDA-MBA-231 breast cancer cells by inducing apoptosis. Especially in MDA-MB-231 cells apoptosis is detected to be triggered by ER stress. The antigrowth effects of Soloxolone methyl were determined using MTT and ATP assays. To identify the mode of cell death (apoptosis/necrosis), fluorescent staining (Hoechst 33342 and Propidium iodide) and caspase-cleaved cytokeratin 18 (M30-antigen) analyses were used. In addition, apoptosis was investigated on gene and protein levels by PCR and Western Blotting. Soloxolone methyl decreased cell viability on cells in a dose and time-dependent manner and induced apoptosis markers. An increase on apoptotic proteins related to endoplasmic reticulum stress (IRE1-α, Bip, CHOP) was also determined in MDA-MB-231 cells. Moreover, an increase of apoptotic gene expressions was determined in both cells treated with Soloxolone methyl. Advance analyses should be performed to elucidate the potential of Soloxolone methyl as an anticancer agent in breast cancer treatment.
作为女性癌症死亡的主要原因之一，各种从天然化合物中分离出来的化疗药物被用于乳腺癌的治疗，因此开发新药的研究仍在继续。有几项研究针对甘草次酸（18βH-甘草次酸）作为一种潜在的抗癌剂，甘草次酸是甘草（甘草根）中的一种次生代谢物。在这项研究中，研究了甘草次酸的半合成衍生物 Soloxolone 甲酯对乳腺癌细胞（MCF-7、MDA-MBA-231）的细胞毒性和凋亡作用。Soloxolone 甲酯通过诱导细胞凋亡，对 MCF-7 和 MDA-MBA-231 乳腺癌细胞均具有细胞毒性。特别是在 MDA-MB-231 细胞中，凋亡是由内质网应激引起的。使用 MTT 和 ATP 测定法来确定 Soloxolone 甲酯的抗增殖作用。为了确定细胞死亡（凋亡/坏死）的模式，使用荧光染色（Hoechst 33342 和碘化丙啶）和 caspase 切割细胞角蛋白 18（M30-抗原）分析。此外，通过 PCR 和 Western Blotting 在基因和蛋白质水平上研究了凋亡。Soloxolone 甲酯以剂量和时间依赖性方式降低细胞活力并诱导凋亡标志物。还确定 MDA-MB-231 细胞中与内质网应激相关的凋亡蛋白（IRE1-α、Bip、CHOP）增加。此外，在两种用 Soloxolone 甲酯处理的细胞中，凋亡基因的表达也增加。应该进行进一步的分析，以阐明 Soloxolone 甲酯作为乳腺癌治疗中抗癌剂的潜力。
