Programa de Pós-graduação em Bioquímica e Biologia Molecular, Departamento de Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Programa de Pós-graduação em Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Instituto Federal de Educação, Ciência e Tecnologia do Rio Grande do Norte, Campus São Gonçalo do Amarante, RN, Brazil.
Int J Biol Macromol. 2020 Nov 1;162:1153-1165. doi: 10.1016/j.ijbiomac.2020.06.100. Epub 2020 Jun 15.
Thrombin triggers cellular responses that are crucial for development and progression of cancer, such as proliferation, migration, oncogene expression and angiogenesis. Thus, biomolecules capable of inhibiting this protease have become targets in cancer research. The present work describes the in vitro antitumor properties of a chondroitin sulfate with anti-thrombin activity, isolated from the Litopenaeus vannamei shrimp (sCS). Although the compound was unable to induce cytotoxicity or cell death and/or cell cycle changes after 24 h incubation, it showed a long-term antiproliferative effect, reducing the tumor colony formation of melanoma cells by 75% at 100 μg/mL concentration and inhibiting the anchorage-independent colony formation. sCS reduced 66% of melanoma cell migration in the wound healing assay and 70% in the transwell assay. The compound also decreased melanin and TNF-α content of melanoma cells by 52% and 75% respectively. Anti-angiogenic experiments showed that sCS promoted 100% reduction of tubular structure formation at 100 μg/mL. These results are in accordance with the sCS-mediated in vitro expression of genes related to melanoma development (Cx-43, MAPK, RhoA, PAFR, NFKB1 and VEGFA). These findings bring a new insight to CS molecules in cancer biology that can contribute to ongoing studies for new approaches in designing anti-tumor therapy.
凝血酶触发的细胞反应对癌症的发展和进展至关重要，如增殖、迁移、癌基因表达和血管生成。因此，能够抑制这种蛋白酶的生物分子已成为癌症研究的目标。本工作描述了从凡纳滨对虾（Litopenaeus vannamei）中分离出的具有抗凝血酶活性的硫酸软骨素（sCS）的体外抗肿瘤特性。尽管该化合物在 24 小时孵育后不能诱导细胞毒性或细胞死亡和/或细胞周期变化，但它表现出长期的抗增殖作用，在 100μg/mL 浓度下可使黑色素瘤细胞的肿瘤集落形成减少 75%，并抑制锚定非依赖性集落形成。sCS 在划痕愈合试验中减少了 66%的黑色素瘤细胞迁移，在 Transwell 试验中减少了 70%。该化合物还使黑色素瘤细胞中的黑色素和 TNF-α含量分别减少了 52%和 75%。抗血管生成实验表明，sCS 在 100μg/mL 时可促进管状结构形成减少 100%。这些结果与 sCS 介导的与黑色素瘤发展相关的基因的体外表达一致（Cx-43、MAPK、RhoA、PAFR、NFKB1 和 VEGFA）。这些发现为 CS 分子在癌症生物学中的作用提供了新的认识，这有助于进行新的抗肿瘤治疗设计方法的研究。
