Anti-Cancer Effect of α-Solanine by Down-Regulating S100P Expression in Colorectal Cancer Cells

Recent Pat Anticancer Drug Discov. 2018;13(2):240-247. doi: 10.2174/1574892813666180329163945.

Abstract

Background: α-Solanine, the most important and active component of Solanum nigrum, was found to have anti-cancer activity on multiple cancer cells. However, its effects on colorectal cancer (CRC) and associated molecular mechanisms remain to be further elucidated.

Objective: In this study, we investigated the anti-cancer effects of α-solanine against CRC cells in vitro and in vivo.

Materials & methods: Cell viability was measured using Cell Counting Kit-8 (CCK-8) assay; cell cycle was analyzed with a Cycletest Plus DNA Reagent Kit; cell apoptosis was detected by flow cytometer; cell migration and invasive ability was determined by Transwell assays; S100P protein expression was also analyzed by western blotting; lentiviral vectors expressing shRNA targeting the S100P gene.

Results: We demonstrated that α-solanine inhibited CRC cell (SW480, SW620 and HT-29) growth as well as migration and invasion, induced cell cycle arrest and apoptosis in vitro, and suppressed tumor growth in vivo. Moreover, we observed that S100P expression was downregulated by α-solanine. Overexpression of S100P partially reversed the α-solanine-induced growth inhibition of CRC cells. Conversely, knockdown of S100P by lentiviral-mediated RNAi resulted in significantly promoting the α-solanine-induced growth inhibition.

Conclusion: These findings suggest that α-solanine is a potential agent for the treatment of CRC, and the anti-tumor effect of α-solanine in the CRC cells may be mediated at least partly by the downregulation of S100P.

Keywords: Anti-tumor effect; S100P; apoptosis; cell-cycle arrest; colorectal cancer; invasion; migration; α-solanine..

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Calcium-Binding Proteins / antagonists & inhibitors*
  • Calcium-Binding Proteins / biosynthesis
  • Calcium-Binding Proteins / genetics
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism*
  • Down-Regulation / drug effects*
  • Down-Regulation / physiology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • HT29 Cells
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Solanine / pharmacology*
  • Solanine / therapeutic use
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Tumor Burden / physiology
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • Calcium-Binding Proteins
  • Neoplasm Proteins
  • S100P protein, human
  • alpha-solanine
  • Solanine