Alpha-solanine inhibits cell proliferation via mitochondrial dysfunction and inhibin synthesis in mouse testis In vitro and In vivo

Abstract

Sertoli and Leydig cells provide key supporting roles in spermatogenesis. Various toxins have been studied in the TM3 and TM4 mouse testis cell lines to identify their regulatory effects. Alpha-solanine (α-solanine), a toxic compound found in the potato, has cytotoxic effects on various cells, including cancer cells. However, the effect of α-solanine on testis function has not been identified. In this study, we verified for the first time the anti-proliferative effect of α-solanine in mouse testes. α-Solanine reduced cell viability in TM3 and TM4 cells and reduced the expression of the cell cycle checkpoint genes Ccnd1 and Ccne1. We also detected changes in the mitochondrial membrane potential (MMP) and in the cytosolic calcium and intracellular signal pathways in both cell lines. α-Solanine induced AKT, P70S6K, S6, ERK1/2, and JNK activation in mouse testis cells. In addition, the inhibition of AKT with a pharmacological inhibitor (LY294002) demonstrated more synergic anti-proliferative effects than in the TM3 and TM4 cell lines treated only with α-solanine. Inha and Inhba mRNA expression also decreased in both cell lines and α-solanine i.p. injected mouse testes. Collectively, the results from this study verify the toxic effects of α-solanine on testes and male reproductive function.