Abstract

Squids are one of the most important commercial marine resources having high human consumption and market value. An Indian squid, Loligo duvauceli is a valuable species among them. They contain ink sacs which are discarded before using them for consumption. This study for the first time reports its potent ability to inhibit angiogenesis in vitro and in vivo. The melanin-free extract (MFI) of squid ink was assessed for antiproliferative effect on cancer and human umbilical vein endothelial (HUVEC) cell lines. Its antiangiogenic activity was investigated in HUVEC-based tube formation and chick chorioallantoic membrane (CAM) assays. The MFI displayed a prominent reduction in the mean vascular density of the CAM membrane, the viability of HUVEC cells, and its tube formation on the Matrigel base. Influence on the expression of angiogenesis effector genes HIF 1 α, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptors (VEGFR), and COX 2 in HUVEC cell line denoted prominent downregulation of HIF 1 α, VEGF, and VEGFR gene expression. Overall, the results indicated a remarkable potential of L. duvauceli ink to serve as a negative mediator of angiogenesis with probable selective HIF1α induced molecular mechanism for exerting its effect. This waste product of sea food processing industry thus presented itself as a promising natural candidate for arresting angiogenesis.

Key words: Anti-angiogenesis, Loligo duvauceli squid, CAM assay, HUVEC cells, vascular endothelial growth factor