Antitumor activity of solamargine in mouse melanoma model: relevance to clinical safety

ABSTRACT

Melanoma is the most aggressive type of skin cancer, and thus it is important to develop new drugs for its treatment. The present study aimed to examine the antitumor effects of solamargine a major alkaloid heteroside present in Solanum lycocarpum fruit. In addition solamargine was incorporated into nanoparticles (NP) of yttrium vanadate functionalized with 3-chloropropyltrimethoxysilane (YVO₄:Eu³⁺:CPTES:SM) to determine antitumor activity. The anti-melanoma assessment was performed using a syngeneic mouse melanoma model B16F10 cell line. In addition, systemic toxicity, nephrotoxic, and genotoxic parameters were assessed. Solamargine, at doses of 5 or 10 mg/kg/day administered subcutaneously to male C57BL/6 mice for 5 days, decreased tumor size and frequency of mitoses in tumor tissue, indicative of a decrease in cell proliferation. Treatments with YVO₄:Eu³⁺:CPTES:SM significantly reduced the number of mitoses in tumor tissue, associated with no change in tumor size. There were no apparent signs of systemic toxicity, nephrotoxicity, and genotoxicity initiated by treatments either with solamargine alone or plant alkaloid incorporated into NP. The animals treated with YVO₄:Eu³⁺:CPTES:SM exhibited significant increase in spleen weight accompanied by no apparent histological changes in all tissues examined. In addition, animals treated with solamargine (10 mg/kg/day) and YVO₄:Eu³⁺:CPTES:SM demonstrated significant reduction in hepatic DNA damage which was induced by tumor growth. Therefore, data suggest that solamargine may be considered a promising candidate in cancer therapy with no apparent toxic effects.

KEYWORDS:

• Solamargine
• inorganic nanoparticle
• skin neoplasms

Acknowledgments

This investigation was supported by the São Paulo Research Foundation (FAPESP; Brazil; grant # [2013/13903-9] and [2019/02641-0]). Ricardo A. Furtado was the recipient of a postdoctoral fellowship from FAPESP (grant # [2013/02744-7]). The authors are also grateful to the National Council for Scientific and Technological Development (CNPq; Brazil; grant# [307856/2012-7] D.C.T.; # [302668/2017-9] E.J.N.) for granting fellowships, as well as to Coordination for the Improvement of Higher Education Personnel (CAPES).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) [302668/2017-9, 307856/2012-7]; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [2013/02744-7, 2013/13903-9, 2019/02641-0].