PO.TB03.01 · 肿瘤生物学
黑色素的新型抗癌机制：对癌细胞黏附、存活和迁移的影响
Novel anticancer mechanisms of melanin: Effects on cancer cell adhesion, survival, and migration
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
黑色素瘤是最致命的皮肤癌，全球每年新诊断330,000例，死亡60,000例。虽然早期黑色素瘤通常可以治疗，但转移性黑色素瘤通常预后不良，死亡率高。
黑色素是通过黑色素生成途径合成的一种色素，据报道具有抗癌作用。然而，其保护作用的分子机制仍知之甚少。我们假设黑色素可能通过降低癌细胞存活和抑制转移潜能来发挥抗癌活性。
本研究使用3种不同的癌细胞系，包括U937（单核细胞）、HTB-11（神经元）和Colo320（结直肠），并采用多种方法的组合，包括计算机分子对接、细胞黏附实验和MTT实验，以评估黑色素对癌细胞黏附、增殖和存活的影响。
结果显示，黑色素以剂量依赖方式降低U937（单核细胞）癌细胞黏附：在较低浓度下，黑色素使细胞黏附增加29.5%，而在较高浓度下，则降低细胞黏附。在HTB-11细胞中，高浓度黑色素使细胞增殖降低48.61%，而在Colo320细胞中，低浓度黑色素显著抑制细胞生长达63%。
数据还显示，黑色素与癌症相关靶蛋白具有强结合亲和力，包括MMP2、MMP9、CDH1和ITGB1，这提示了黑色素与已知癌症靶蛋白协同调控癌症生长的可能分子和遗传机制。
总之，这些发现提示了黑色素可能调控癌细胞存活、黏附和迁移的新型分子途径。总的来说，本研究为黑色素作为一种具有差异性、剂量依赖性作用的潜在抗癌剂提供了新证据，突显了其作为靶向多种癌症类型的治疗先导物的相关性。
D.L.就职于美国纽约州Manhasset的Manhasset Secondary School。W.Z.就职于美国纽约州Jericho的SCI research institute。
查看英文原文 English abstract
Melanoma is the deadliest form of skin cancer, with 330,000 new cases diagnosed and 60,000 deaths globally each year. While early-stage melanoma is often treatable, metastatic melanoma usually has poor prognosis with a high mortality rate.
Melanin, a pigment synthesized through the melanogenesis pathway, has been reported to exert anti-cancer effects. However, the molecular mechanisms underlying its protective role remain poorly understood. We hypothesize that melanin may exert anticancer activity by reducing cancer cell survival and suppressing metastatic potential.
This study uses 3 different cancer cell lines, including U937 (monocytic), HTB-11 (neuronal), and Colo320 (colorectal), and utilizes a combination of methods, including in silico molecular docking, cell attachment assays, and MTT assays, to evaluate the effects of melanin on cancer cell adhesion, proliferation, and survival.
The results revealed that melanin decreased U937 (monocytic) cancer cell adhesion in a dose dependent manner: at a lower concentration, melanin increased cell adhesion by 29.5%, while in a higher concentration, it decreased cell adhesion. In HTB-11 cells, high concentration of melanin decreased cell proliferation by 48.61%, while in Colo320 cells, low concentration of melanin significantly suppressed cell growth by 63%.
Data also showed that melanin has a strong binding affinity to cancer-related target proteins, including MMP2, MMP9, CDH1, and ITGB1, the possible molecular and genetic mechanisms of melanin in working with known cancer target proteins to regulate cancer growth.
In conclusion, these findings suggest novel molecular pathways by which melanin may regulate cancer cell survival, adhesion, and migration. Collectively, this study provides new evidence for melanin as a potential anticancer agent with differential, dose-dependent effects, underscoring its relevance as a therapeutic lead for targeting diverse cancer types.
D.L. is with Manhasset Secondary School, Manhasset, NY, USA. W.Z. is with SCI research institute, Jericho, NY, USA
利益披露 Disclosure
D. Liu, None..
W. Zhu, None.