Center for Biotechnology and Interdisciplinary Sciences and Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, NY 12180, United States; Department of Chemistry and Chemical Biology and Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, NY 12180, United States; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, NY 12180, United States.
Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, NY 12180, United States.
Bioorg Med Chem. 2022 Jul 1;65:116787. doi: 10.1016/j.bmc.2022.116787. Epub 2022 May 4.
Sophorolipids (SLs) are biosurfactants synthesized as secondary metabolites by non-pathogenic yeasts and other microorganisms. They are members of glycolipid microbial surfactant family that consists of a sophorose polar head group and, most often, an ω-1 hydroxylated fatty acid glycosidically linked to the sophorose moiety. Since the fermentative production of SLs is high (>200 g/L), SLs have the potential to provide low-cost therapeutics. Natural and modified SLs possess anti-cancer activity against a wide range of cancer cell lines such as those derived from breast, cervical, colon, liver, brain, and the pancreas. Corresponding data on their cytotoxicity against noncancerous cell lines including human embryo kidney, umbilical vein, and mouse fibroblasts is also discussed. These results are compiled to elucidate trends in SL-structures that lead to higher efficacy against cancer cell lines and lower cytotoxicity for normal cell lines. While extrapolation of these results provides some insights into the design of SLs with optimal therapeutic indices, we also provide a critical assessment of gaps and inconsistencies in the literature as well as the lack of data connecting structure-to-anticancer and cytotoxicity on normal cells. Furthermore, SL-mechanism of action against cancer cell lines, that includes proliferation inhibition, induction of apoptosis, membrane disruption and mitochondria mediated pathways are discussed. Perspectives on future research to develop SL anticancer therapeutics is discussed.
槐糖脂（SLs）是由非致病性酵母和其他微生物作为次级代谢产物合成的生物表面活性剂。它们是糖脂微生物表面活性剂家族的成员，由一个槐糖极性头基团和，最常见的，一个ω-1 羟化脂肪酸糖苷键连接到槐糖部分。由于 SLs 的发酵生产效率很高（>200 g/L），因此 SLs 有可能提供低成本的治疗方法。天然和修饰的 SLs 对广泛的癌细胞系具有抗癌活性，例如来自乳腺、宫颈、结肠、肝、脑和胰腺的癌细胞系。还讨论了它们对非癌细胞系（包括人胚肾、脐静脉和小鼠成纤维细胞）的细胞毒性的相应数据。这些结果的汇编旨在阐明导致对癌细胞系更高疗效和对正常细胞系更低细胞毒性的 SL 结构趋势。虽然这些结果的推断为设计具有最佳治疗指数的 SL 提供了一些见解，但我们还对文献中的差距和不一致以及缺乏将结构与抗癌和正常细胞毒性联系起来的数据进行了批判性评估。此外，还讨论了 SL 对癌细胞系的作用机制，包括增殖抑制、诱导细胞凋亡、破坏细胞膜和线粒体介导的途径。还讨论了开发 SL 抗癌治疗的未来研究前景。
