Project's information

Project's title Metabolites from brown algae as potential compounds for the preventing of carcinogenesis induced by chemical and physical factors
Project’s code QTRU01.06/21-22
Research hosting institution Nha Trang Institute of Technology Research and Application
Coordinating unit, co-chair The Russian Foundation for Basic Research (RFBR)
Project leader’s name PhD. Huynh Hoang Nhu Khanh and Roza Vladimirovna Usoltseva
Project duration 01/05/2021 - 30/11/2023
Project’s budget 200 million VND
Classify Excellent
Goal and objectives of the project

To isolate, establish the structure of metabolites (galactofucans and phlorotannins) from brown algae of Vietnamese and Far Eastern brown algae, determine their effect on the neoplastic cell transformation induced by chemical and physical carcinogenic factors, and establish the molecular mechanism of cancer-preventive action of substances with the highest biological activity

Main results

The task was to extract, segment and determine the composition of phlorotannins from 05 species of Vietnamese brown seaweed (S. duplicatum, S. feldmannii, S. microcystum, S. oligocystum, S. serratum) and 01 species of Russian brown seaweed. (Costaria costata). At the same time, we extracted, fractionated and determined some structural characteristics of galactofucan from 03 species of Vietnamese brown seaweed (S. microcystum, S. oligocystum, S. serratum) and 01 species of Russian brown seaweed (Alaria angusta).
Ability to prevent the growth of cancer cells under the influence of chemical agents (EGF, TPA) or physical agents (X-rays) of compounds extracted from brown seaweed (fucoidans and phlorotannins) has been studied. The results demonstrated that phlorotannin CcPh at concentrations of 10, 20, and 40 μg/mL inhibited EGF-induced neoplastic transformation of JB6 Cl41 mouse epidermal cells by 46, 78, and 92% and inhibited inhibited TPA-induced neoplastic transformation by 59, 82 and 84%, respectively. Thus, phlorotannin CcPh from C. costata was studied to have a dose-dependent cancer prevention effect against neoplastic transformation of JB6 Cl41 cells. Galactofucan 1AaF2 fractions inhibited cell growth at 27, 64 and 95% compared to the control (not treated with the compound) at concentrations of 50, 100 and 200 μg/mL, respectively; and this inhibition rate of compound 1AaF2-HMP is 42, 61 and 90%, respectively, at the same concentration.
The ability to prevent the growth of the SK-MEL-28 cancer cell line under the influence of a chemical agent (EGF) when treated with fucoidan fractions showed that at concentrations of 200-400 μg/mL the colony formation is almost completely prevented. Fucoidan at lower concentrations (50 μg/mL and 100 μg/mL) slightly inhibited colony formation with inhibition rates of 12 and 23% for 1AaF2, and 31 and 38% for 1AaF2-, respectively, HMP.
Phlorotannin CcPh demonstrated strong inhibition of the growth of HT-29 and HCT-116 cancer cells while only requiring an irradiation dose of 2 Gy. Combined treatment of cells with X-rays (2 Gy) and CcPh (5, 10, and 20 μg/mL) reduced the colony counts of HT-29 cells by 28, 39, and 41% and of HCT-116 by 15, 24, and 40%, respectively, compared with irradiated cells.
The results showed that CcPh at non-toxic concentrations inhibits AKT kinase (Thr308) phosphorylation, GSK-3β protein and cell cycle protein activation in a concentration-dependent manner, thereby preventing X-ray-induced neoplastic transformation of normal cells into tumor cells.

Novelty and actuality and scientific meaningfulness of the results

The results of the mission evaluated the ability of the obtained compounds fucoidan and phlorotannin to prevent cancer by chemical and physical agents.

Products of the project
- Publications:
Structure and chemopreventive activity of fucoidans from the brown alga Alaria angusta (2023), Anastasia O Zueva, Roza V Usoltseva, Olesya S Malyarenko, Valerii V Surits, Artem S Silchenko, Stanislav D Anastyuk, Anton B Rasin, Huynh Hoang Nhu Khanh, Pham Duc Thinh, Svetlana P Ermakova, International Journal of Biological Macromolecules, 255, 648 - 657 https://doi.org/10.1016/j.ijbiomac.2022.11.127.
Recommendations

Conclusion:
Research the mechanism of action of active ingredient groups on the ability to inhibit the survival rate of cancer cells when affected by chemical or physical factors, research the activation process of proteins related to cancer cells. The apotosis pathway is an approach that approaches the possibility of their application in treating or supporting the treatment of cancer. This research direction needs to continue to be implemented on groups of active ingredients extracted from seaweed in particular and compounds of natural origin in general.
The foreign partner is a strong and experienced research group in the field of research on fucoidan, polyphenols and cytotoxic activity tests, determining the mechanism of action of groups of substances... So it is recommended to maintain and develop relationships with partners to continue cooperation, scientific exchange and improve the research capabilities of domestic research staff.
Suggestion:
Fucoidan and phlorotannins from brown seaweed are groups of compounds with diverse and extremely complex structures. Nowadays, with the support of enzymes - specific bond cutting tools and modern analytical methods, the chemical structure and the relationship between structure and biological activity of polysaccharides are gradually being understood clearly. Therefore, we propose to continue to focus on researching small segments as well as the comprehensive structure of groups of compounds obtained from seaweed, and evaluate the impact of the compounds obtained on cell lines cancer when influenced by different groups of carcinogens, including chemical, physical and biological factors. The results of the mission evaluated the ability of the obtained compounds fucoidan and phlorotannin to prevent cancer by chemical and physical agents.

Images of project
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