Assessment of Potential Anticancer Activity of Brown Seaweed Compounds Using Zebrafish Phenotypic Assay

Abstract

Despite the extensive work on anticancer drug discovery, the number of potent lead compounds that enter the preclinical and clinical trials thus far is still low due to the poor selectivity and understanding in pharmacodynamics. In view of the homology between zebrafish embryogenesis and carcinogenesis in human, zebrafish embryos can be used in the screening platform to elucidate the molecular targets of potential anticancer compounds. In the present study, the possible targets modulating the potential anticancer effects of selected brown seaweed-derived compounds (ie alginate, fucoidan, phloroglucinol, fucosterol, and fucoxanthin) were examined. Teratogenic effects induced by the compounds were observed after 72 hours post-fertilization. Fucoidan, phloroglucinol, and fucosterol were observed to significantly reduce the pigmentation of the zebrafish in a dose-dependent manner at low concentrations (fucoidan, <60 µg/mL; phloroglucinol, <10 µg/mL; fucosterol, <3 µg/mL). On the other hand, embryos treated with fucoxanthin at 200 µg/mL and 300 µg/mL exhibited either phenotypes of curved trunk or bent tail. Further validation work using dual antiplatelet therapy (DAPT) and dorsomorphin as positive controls suggest that fucoxanthin might target the Notch and bone morphogenetic protein (BMP) pathways, respectively. Findings from this exploratory study henceforth have demonstrated the utility of zebrafish embryo to accelerate the discovery of potential compounds for targeted anticancer therapy.

Cytotoxicity of Seaweed Compounds, Alone or Combined to Reference Drugs, against Breast Cell Lines Cultured in 2D and 3D

“…This study explored the cytotoxic effects of five brown seaweed compounds alone and combined with two reference drugs in a panel of breast cell lines, representing three BC subtypes and including a non-tumoral breast cell line. The study is justified considering that seaweed compounds, especially those from brown seaweeds, have been showing anticarcinogenic activities in many in vitro and in vivo studies related to many types of cancers, including BC [ 22 , 24 , 54 , 109 , 110 ]. The effects of combining seaweed compounds plus chemotherapeutic drugs are also relevant to explore, taking into consideration their implications in clinical scenarios.…”

Antioxidant activity and zebrafish teratogenicity of hydroalcoholicMoringa oleiferaL. leaf extracts

“…In term of safety for human consumption, only powdered MO leaves was reported safe up to 50 g per day in a single dose, or 8 g per day for 40 days, and none of the solvents-extracted MO leaves extract has been tested in human (Stohs and Hartman, 2015). Zebrafish phenotypic assay also widely used in the screening of the bioactive substances with anticancer properties, due to homologous between zebrafish embryogenesis and human carcinogenesis (Rusdi et al , 2019; Parng et al , 2002). The embryo that survived in the aqueous methanol extract at the concentration of 300 µg/mL was positive for yolk sac oedema and bent tail.…”

“…Yolk sac oedema in zebrafish might be due to the impairment of the blood flow or fluid (Belair et al , 2001). The bent tail observed can be associated with the ability in interfering BMP proteins and its pathway to suppress tumour metastasis (Rusdi et al , 2019). This suggests that aqueous methanolic extract might possess anticancer properties and further studies are needed to explore the potent anticancer activity.…”

Toxicity Effect of Bougainvillea glabra (Paper Flower) Water Extracts on Zebrafish Embryo

“…In anticancer drug discovery, zebrafish phenotypic assay is applied for the rapid screening of bioactive compounds with anticancer properties due to the high degree of homology between human carcinogenesis and zebrafish embryogenesis [7,12,17]. The reason of hypopigmentation observed in the embryo treated with the purple bract extract is unknown.…”

“…In this study, chorionated embryos were used to avoid high mortality and dysmorphology as a result of the chorion removal procedure, and developmental defects were compared and normalized with the negative control (untreated, only E3 media). The experiment was considered valid if the control groups did not show more than 10% of lethality and defect on the 3 rd day after fertilization [12]. The extract concentrations used were based on the Organization for Economic Co-operation and Development guideline [13].…”