Efficacy of marine biomolecules on angiogenesis by targeting hypoxia inducible factor/vascular endothelial growth factor signaling in zebrafish model

Abstract

Marine resources are notably explored for their unique biomolecules that have been designed to be drug targets for their immense potential against various pathologies. These biomolecules are mostly secondary metabolites from different species that include sponges, tunicates, echinoderms, ascidians, algae, and marine symbionts.Among the various biological activities of the marine biomolecules, antiangiogenic property has gained much significance in alternate therapy for treatment against cancer. Hypoxia inducible factor (HIF) and vascular endothelial growth factor (VEGF) are the prime signaling pathways related to angiogenesis that are exclusively designated as markers for critical selection of novel inhibitors. This is mainly due to their importance in tumor induction and regulatory control over other interlinked pathways involved in cancer. Small molecular drug screening using the zebrafish model has been an advantage in cancer research in recent times. This review addresses the importance of marine biomolecules and their antiangiogenic efficacy by targeting HIF/VEGF pathways experimented in the zebrafish model in the last decade. Thus, it would provide more clear insights into the role of biomolecules in alternative cancer therapy.

Noscapine modulates hypoxia‐induced angiogenesis and hemodynamics: Insights from a zebrafish model investigation

“…The detrimental effect of noscapine on embryo morphology was due to defective vascular development. Similar phenotypic defects were reported in some studies evaluating the antiangiogenicity of berberine and indole‐ 3 ‐propionic acid (Jagadeeshan et al, 2017; Nathan et al, 2023). Interestingly, there was a rare phenotype with tail truncation but still had good blood flow and heart rate.…”

“…The adult wild‐type zebrafish were purchased from local vendors in Chennai, India. They were maintained at a species‐specific condition and nourished twice a day with flakes and tubifex worms (Nathan et al, 2023). The embryos were obtained through the natural breeding of male and female fish at a 2:1 ratio, and the stages were fixed as hours postfertilization (hpf) (de Melo Martins et al, 2022; Kimmel et al, 1995; Nathan et al, 2023; Westerfield, 2000).…”

“…They were maintained at a species‐specific condition and nourished twice a day with flakes and tubifex worms (Nathan et al, 2023). The embryos were obtained through the natural breeding of male and female fish at a 2:1 ratio, and the stages were fixed as hours postfertilization (hpf) (de Melo Martins et al, 2022; Kimmel et al, 1995; Nathan et al, 2023; Westerfield, 2000). All the experiments were approved by the Institutional Animal Ethics Committee (Certificate number: BRULAC/SDCH/SIMATS/IAEC/06‐2023/14).…”

“…The video was examined and the cardiac function was assessed using Fiji ImageJ software, a Java‐based open‐source image processing program. The captured videos were modified to make them compatible with ImgaeJ, and the heart rate was determined using the same procedures as in our earlier work (Nathan et al, 2023).…”

“…Total RNA was extracted from embryos treated with the hypoxic group (CoCl 2 50 µM and CoCl 2 50 µM + noscapine 50 μM), normoxic group (noscapine 1, 10, and 50 μM), VEGFR2 inhibitor (SU5416 1 µM) group, and DMSO control group at 72 hpf, in accordance with the manufacturer's instructions. Reverse transcription of the RNA was done, and real‐time PCR was performed in compliance with our established procedures (Nathan et al, 2023). Primer sequences used for the investigation were purchased from Sigma‐Aldrich (Table 1).…”