α-Chaconine and α-Solanine Inhibit RL95-2 Endometrium Cancer Cell Proliferation by Reducing Expression of Akt (Ser473) and ERα (Ser167)

Nutrients. 2018 May 25;10(6):672. doi: 10.3390/nu10060672.

Abstract

The aim of this study is to investigate the potential inhibitory effect of α-chaconine and α-solanine on RL95-2 estrogen receptor (ER) positive human endometrial cancer cell line and to identify the effect of these glycoalkaloids on the Akt signaling and ERα. The cell proliferation profiles and the cytotoxicity studies were performed by Real-Time Cell Analyzer (xCELLigence) and compared with Sulphorhodamine B (SRB) assay. The effects of α-chaconine (2.5, 5, 10 µM), α-solanine (20, 30, 50 µM), API-1 (25 µM) and MPP (20 µM) effects on Akt (Ser473) and ERα (Ser167) expressions evaluated by Western blot and qPCR method. Their IC50 values were as α-chaconine (4.72 µM) < MPP (20.01 µM) < α-solanine (26.27 µM) < API-1 (56.67 µM). 10 μM α-chaconine and 20, 30 and 50 μM α-solanine were effective in decreasing p-Akt(Ser473)/Akt ratio compared to positive control API-1. When the p-ERα/ERα ratios were evaluated, it was observed that α-chaconine (2.5, 5, 10 μM) and α-solanine (50 μM) were as effective as the specific ERα inhibitor MPP in reducing the ratio of p-ERα/ERα compared to the control group. In conclusion, it has been shown that the proliferation of α-chaconine and α-solanine in human endometrial carcinoma cells reduces the expression and activity of the Akt and ERα signaling pathway.

Keywords: API-1; Akt; ERα; MPP dihydrochloride; RL95-2; Solanum tuberosum L.; endometrium cancer; steroidal glycoalkaloids; α-chaconine; α-solanine.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / enzymology
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Solanine / analogs & derivatives*
  • Solanine / pharmacology
  • Time Factors

Substances

  • Antineoplastic Agents, Phytogenic
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • alpha-solanine
  • Solanine
  • alpha-chaconine
  • Proto-Oncogene Proteins c-akt