Unit of Genetic Engineering and Biotechnology, Faculty of Science, Mansoura University, El-Gomhoria Street, Mansoura, 35516, Egypt.
Microbial Activity Unit, Department of Microbiology, Soils, Water and Environment Research Institute, Agricultural Research Center, Giza12619, Egypt.
Curr Top Med Chem. 2024;24(24):2141-2160. doi: 10.2174/0115680266300091240730111333.
This study explores the potential of the endophytic fungus Aureobasidium pullulans AKW for melanin production and its anticancer activity.
We report a significant achievement: AKW synthesized 4.89 g/l of melanin in a simple fermentation medium devoid of tyrosine, a precursor typically required for melanin biosynthesis. This suggests a potentially novel pathway for melanin production compared to previous studies relying on complex media and tyrosine. Furthermore, the isolated and characterized melanin exhibited promising selectivity as an anti-cancer agent. It triggered apoptosis in A431 cancer cells, demonstrating some selectivity compared to normal cells. This selectivity was confirmed by IC values and further supported by gene expression changes in A431 cells. Melanin treatment downregulated the anti-apoptotic Bcl2 gene while upregulating pro-apoptotic Bax and p53 genes, indicating its ability to induce programmed cell death in cancer cells.
Our results demonstrate that AKW-derived melanin exhibits cytotoxic effects against A431, HEPG2, and MCF7 cell lines. Interestingly, the present fungal strain synthesized melanin in a simple medium without requiring precursors.
The selective activity of the current melanin towards cancer cells, its ability to induce apoptosis, and its relatively low toxicity towards normal cells warrant further investigation for its development as a novel therapeutic option.
本研究探索了内生真菌节菱孢 Aureobasidium pullulans AKW 产生黑色素的潜力及其抗癌活性。
我们报告了一项重大成就：AKW 在缺乏酪氨酸的简单发酵培养基中合成了 4.89 g/L 的黑色素，酪氨酸是黑色素生物合成通常所需的前体。与以前依赖复杂培养基和酪氨酸的研究相比，这表明了一种生产黑色素的潜在新途径。此外，分离和表征的黑色素作为一种抗癌剂表现出有希望的选择性。它在 A431 癌细胞中引发细胞凋亡，与正常细胞相比表现出一定的选择性。IC 值证实了这种选择性，并且 A431 细胞中的基因表达变化进一步支持了这一点。黑色素处理下调了抗凋亡基因 Bcl2，而上调了促凋亡基因 Bax 和 p53，表明其能够诱导癌细胞程序性死亡。
我们的结果表明，AKW 衍生的黑色素对 A431、HEPG2 和 MCF7 细胞系具有细胞毒性作用。有趣的是，目前的真菌菌株在简单的培养基中合成黑色素，而不需要前体。
当前黑色素对癌细胞的选择性活性、诱导细胞凋亡的能力以及对正常细胞的相对低毒性使其有必要进一步研究作为一种新的治疗选择。
