Hypoxia protects against the cell death triggered by oxovanadium–galactomannan complexes in HepG2 cells

Autor: Meyenberg Cunha-de Padua, Monique, Noleto, Guilhermina Rodrigues, de Oliveira Petkowicz, Carmen Lucia, Cadena, Silvia Maria Suter Correia, Bost, Frédéric, Pouysségur, Jacques, Mazure, Nathalie M.
Přispěvatelé: Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Cellular and Molecular Biology Letters
Cellular and Molecular Biology Letters, Springer Verlag (Germany), 2019, 24, ⟨10.1186/s11658-019-0135-3⟩
Cellular & Molecular Biology Letters
Cellular & Molecular Biology Letters, Vol 24, Iss 1, Pp 1-11 (2019)
ISSN: 1425-8153
1689-1392
DOI: 10.1186/s11658-019-0135-3⟩
Popis: International audience; Background: Polysaccharides from various sources have been used in traditional medicine for centuries. The beneficial pharmacological effects of plant-derived polysaccharides include anti-tumor activity. Methods: Here, we evaluated the anti-cancer effect of the MSAGM:VO complex under hypoxic conditions (1% oxygen). MSAGM:VO is a complex of the hydrolysate of galactomannan (MSAGM) from Schizolobium amazonicum with oxovanadium (IV/ V). The hepatocellular carcinoma (HCC) cell line HepG2 was selected as HCC are one of the most hypoxic solid tumors. Results: Our results showed that the strong apoptotic activity of MSAGM:VO observed in HepG2 cells under normoxic conditions was completely lost under hypoxic conditions. We found a dynamic balance between the pro-and anti-apoptotic members of the Bcl-2 protein family. The expressions of anti-apoptotic Mcl-1 and Bcl-X L increased in hypoxia, whereas the expression of pro-apoptotic Bax decreased. MSAGM:VO strongly induced autophagy, which was previously characterized as a pro-survival mechanism in hypoxia. These results demonstrate total elimination of the anti-cancer activity of MSAGM:VO with activation of autophagy under conditions of hypoxia. Conclusion: Although this study is a proof-of-concept of the impact of hypoxia on the potential of polysaccharides, further study is encouraged. The anti-tumor activity of polysaccharides could be achieved in normoxia or through raising the activity of the immune system. In addition, combination strategies for therapy with anti-autophagic drugs could be proposed.
Databáze: OpenAIRE
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