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In vitro antitumor and anti-angiogenic activities of a shrimp chondroitin sulfate
Lais C G F Palhares1, Jefferson S Barbosa2, Kátia C Scortecci3
1Programa de Pós-graduação em Bioquímica e Biologia Molecular, Departamento de Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Abstract:
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.
Insights
A novel chondroitin sulfate from shrimp (sCS) demonstrates significant anti-cancer properties by inhibiting melanoma cell proliferation, migration, and angiogenesis. This marine-derived compound offers a promising avenue for developing new anti-tumor therapies.
Area of Science:
- Marine Biology
- Biochemistry
- Cancer Research
Background:
- Thrombin plays a critical role in cancer progression, driving proliferation, migration, oncogene expression, and angiogenesis.
- Inhibiting thrombin activity is a key strategy in cancer research, necessitating the identification of novel biomolecules.
- Chondroitin sulfate (CS) molecules are being explored for their potential therapeutic applications.
Purpose of the Study:
- To investigate the in vitro antitumor properties of shrimp-derived chondroitin sulfate (sCS) with anti-thrombin activity.
- To evaluate the effects of sCS on melanoma cell proliferation, migration, colony formation, and angiogenesis.
- To analyze the impact of sCS on the expression of key melanoma development genes.
Main Methods:
- In vitro assays were used to assess cytotoxicity, cell cycle changes, and long-term antiproliferative effects on melanoma cells.
- Wound healing and transwell assays were employed to measure melanoma cell migration.
- Anti-angiogenic potential was evaluated by observing tubular structure formation.
- Gene expression analysis was performed to examine the in vitro effects of sCS on genes related to melanoma development.
Main Results:
- sCS exhibited a significant long-term antiproliferative effect, reducing melanoma tumor colony formation by 75% and inhibiting anchorage-independent colony formation.
- sCS markedly reduced melanoma cell migration, with a 66% decrease in wound healing and 70% in transwell assays.
- The compound demonstrated potent anti-angiogenic activity, causing a 100% reduction in tubular structure formation, and decreased melanin and TNF-α content.
- sCS modulated the in vitro expression of genes crucial for melanoma development, including Cx-43, MAPK, RhoA, PAFR, NFKB1, and VEGFA.
Conclusions:
- Shrimp-derived chondroitin sulfate (sCS) possesses significant in vitro antitumor properties, including antiproliferative, anti-migratory, and anti-angiogenic effects.
- sCS influences the expression of key genes involved in melanoma development, suggesting a multifaceted mechanism of action.
- These findings highlight the potential of marine-derived CS molecules as novel therapeutic agents for anti-tumor strategies.
