Department of Chemistry, University of Alabama at Birmingham, 901, 14th Street S, Birmingham, AL 35294, USA.
Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard, VH 566A, P.O. Box 202, Birmingham, AL 35294, USA.
Mar Drugs. 2019 Jul 27;17(8):443. doi: 10.3390/md17080443.
Non-melanoma skin cancer is one of the major ailments in the United States. Effective drugs that can cure skin cancers are limited. Moreover, the available drugs have toxic side effects. Therefore, skin cancer drugs with less toxic side effects are urgently needed. To achieve this goal, we focused our work on identifying potent lead compounds from marine natural products. Five lead compounds identified from a class of pyrroloiminoquinone natural products were evaluated for their ability to selectively kill squamous cell carcinoma (SCC13) skin cancer cells using an MTT assay. The toxicity of these compounds was also evaluated against the normal human keratinocyte HaCaT cell line. The most potent compound identified from these studies, was further evaluated for its ability to inhibit cancer cell migration and invasion using a wound-healing assay and a trans-well migration assay, respectively. To investigate the molecular mechanism of cell death, the expression of apoptotic and autophagy proteins was studied in treated cells compared to untreated cells using western blot. Our results showed that all five compounds effectively killed the SCC13 cells, with compound being the most effective. Compound was more effective in killing the SCC13 cells compared to HaCaT cells with a two-fold selectivity. The migration and the invasion of the SCC13 cells were also inhibited upon treatment with compound . The expression of pro-apoptotic and autophagy proteins with concomitant downregulation in the expression of survival proteins were observed in treated cells. In summary, the marine natural product analog compound showed promising anticancer activity against human skin cancer cells and holds potential to be developed as an effective anticancer agent to combat skin cancer.
非黑色素瘤皮肤癌是美国的主要疾病之一。能够治愈皮肤癌的有效药物有限。此外，现有的药物有有毒的副作用。因此，急需具有较少毒副作用的皮肤癌药物。为了实现这一目标，我们专注于从海洋天然产物中寻找有潜力的先导化合物。从一类吡咯并亚氨基醌天然产物中鉴定出的 5 种先导化合物，通过 MTT 测定法评估其选择性杀死鳞状细胞癌 (SCC13) 皮肤癌细胞的能力。还评估了这些化合物对正常人类角质形成细胞 HaCaT 细胞系的毒性。从这些研究中鉴定出的最有效化合物 ，进一步评估了其抑制癌细胞迁移和侵袭的能力，分别使用划痕愈合测定法和 Transwell 迁移测定法。为了研究细胞死亡的分子机制，使用 Western blot 研究了与未经处理的细胞相比， 处理的细胞中凋亡和自噬蛋白的表达。我们的结果表明，所有 5 种化合物都能有效地杀死 SCC13 细胞，其中化合物 最为有效。与 HaCaT 细胞相比，化合物 对 SCC13 细胞的杀伤效果更为显著，其选择性为 2 倍。SCC13 细胞的迁移和侵袭也被 处理所抑制。在 处理的细胞中观察到促凋亡和自噬蛋白的表达，同时存活蛋白的表达下调。总之，海洋天然产物类似物化合物 对人皮肤癌细胞表现出有希望的抗癌活性，有潜力开发为有效的抗癌药物，以对抗皮肤癌。
