In vitro and in vivo antitumor effects of the VO-chrysin complex on a new three-dimensional osteosarcoma spheroids model and a xenograft tumor in mice
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Osteosarcoma (OS) is the most common primary tumor of bone, occurring predominantly in the second decade of life. High-dose cytotoxic chemotherapy and surgical resection have improved prognosis, with long-term survival for patients with localized disease. Vanadium is an ultra-trace element that after being absorbed accumulates in bone. Besides, vanadium compounds have been studied during recent years to be considered as representative of a new class of non-platinum antitumor agents. Moreover, flavonoids are a wide family of polyphenolic compounds that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, the in vitro and in vivo effects of an oxidovanadium(IV) complex with the flavonoid chrysin on the new 3D human osteosarcoma and xenograft osteosarcoma mice models. The pharmacological results show that VOchrys inhibited the cell viability affecting the shape and volume of the spheroids and VOchrys suppressed MG-63 tumor growth in the nude mice without inducing toxicity and side effects. As a whole, the results presented herein demonstrate that the antitumor action of the complex was very promissory on human osteosarcoma models, whereby suggesting that VOchrys is a potentially good candidate for future use in alternative antitumor treatments.
KeywordsOsteosarcoma Vanadium Xenograft mice Spheroids Flavonoids
This work was partly supported by UNLP (11X/690), CONICET (PIP 1125), and ANPCyT (PICT 2014-2223, PPL2-2011-0008, and PME 2006-068) from Argentina. IEL and SBE are members of the Carrera del Investigador, CONICET, Argentina. JFCV is fellowship from CONICET, Argentina. The authors would like to thank to Prof. Dr. Adriana Massone (FCV, UNLP) for the management work with the tumor histopathology.
- 1.Nielsen FH (1995) Metal ions in biological systems: volume 31: vanadium and its role for life. CRC Press, Boca RatonGoogle Scholar
- 5.Etcheverry SB, Barrio DA (2007) Vanadium and bone: relevance of vanadium compounds in bone cells. In: Kustin K, Costa Pesoa J, Crans DC (eds) Vanadium: the versatile metal, chap 15, vol 974. American chemical society series, pp 204–216Google Scholar
- 20.Naso L, Ferrer EG, Lezama L et al (2010) Role of oxidative stress in the antitumoral action of a new vanadyl(IV) complex with the flavonoid chrysin in two osteoblast cell lines: relationship with the radical scavenger activity. J Biol Inorg Chem 15:889–902. doi: 10.1007/s00775-010-0652-z CrossRefPubMedGoogle Scholar
- 23.National Research Council (2011) Guide for the Care and Use of Laboratory Animals. National Academies Press, Washington, D.C.Google Scholar
- 35.Reytman L, Braitbard O, Hochman J, Tshuva EY (2015) Highly effective and hydrolytically stable vanadium(V) amino phenolato antitumor agents, pp 1–9. doi: 10.1021/acs.inorgchem.5b02519
- 39.Santini M, Rainaldi G, Indovina P (2000) Apoptosis, cell adhesion and the extracellular matrix in the three-dimensional growth of multicellular tumor spheroids. Crit Rev Oncol 36:75–87Google Scholar
- 50.Samanta S, Swamy V, Suresh D et al (2008) Protective effects of vanadium against DMH-induced genotoxicity and carcinogenesis in rat colon: removal of O(6)-methylguanine DNA adducts, p53 expression, inducible nitric oxide synthase downregulation and apoptotic induction. Mutat Res 650:123–131. doi: 10.1016/j.mrgentox.2007.11.001 CrossRefPubMedGoogle Scholar
- 51.Chakraborty T, Ghosh S, Datta S et al (2003) Vanadium suppresses sister-chromatid exchange and DNA-protein crosslink formation and restores antioxidant status and hepatocellular architecture during 2-acetylaminofluorene-induced experimental rat hepatocarcinogenesis. J Exp Ther Oncol 3:346–62Google Scholar
- 52.Bishayee A, Chatterjee M (1994) Inhibition of altered liver cell foci and persistent nodule growth by vanadium during diethylnitrosamine-induced hepatocarcinogenesis in rats. Anticancer Res 15:455–61Google Scholar