Abusara Osama H, Ibrahim Ali I M, Issa Hamzah, Hammad Alaa M, Ismail Worood H
Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.
Aurum Biotech, Amman 11941, Jordan.
Curr Issues Mol Biol. 2023 Mar 6;45(3):2170-2181. doi: 10.3390/cimb45030139.
Aldehyde dehydrogenase (ALDH) enzymes are involved in the growth and development of several tissues, including cancer cells. It has been reported that targeting the ALDH family, including the ALDH1A subfamily, enhances cancer treatment outcomes. Therefore, we aimed to investigate the cytotoxicity of ALDH1A3-affinic compounds that have been recently discovered by our group, on breast (MCF7 and MDA-MB-231) and prostate (PC-3) cancer cell lines. These compounds were investigated on the selected cell lines as single treatments and in combination with doxorubicin (DOX). Results showed that the combination treatment experiments of the selective ALDH1A3 inhibitors (compounds and ) at variable concentrations with DOX resulted in significant increases in the cytotoxic effect on the MCF7 cell line for compound , and to a lesser extent for compound on the PC-3 cell line, compared to DOX alone. The activity of compounds and as single treatments on all cell lines was found to be non-cytotoxic. Therefore, our findings showed that the investigated compounds have a promising potential to target cancer cells, possibly via an ALDH-related pathway, and sensitize them to DOX treatment.
醛脱氢酶（ALDH）参与包括癌细胞在内的多种组织的生长和发育。据报道，靶向ALDH家族，包括ALDH1A亚家族，可提高癌症治疗效果。因此，我们旨在研究我们团队最近发现的ALDH1A3亲和化合物对乳腺癌（MCF7和MDA-MB-231）和前列腺癌（PC-3）细胞系的细胞毒性。这些化合物作为单一处理剂以及与阿霉素（DOX）联合，在选定的细胞系上进行了研究。结果表明，与单独使用DOX相比，选择性ALDH1A3抑制剂（化合物 和 ）在不同浓度下与DOX联合处理实验，对MCF7细胞系中化合物 的细胞毒性作用显著增加，对PC-3细胞系中化合物 的细胞毒性作用增加程度较小。发现化合物 和 作为单一处理剂对所有细胞系的活性均无细胞毒性。因此，我们的研究结果表明，所研究的化合物有可能通过与ALDH相关的途径靶向癌细胞，并使它们对DOX治疗敏感。
