α-Tomatine inhibits growth and induces apoptosis in HL-60 human myeloid leukemia cells.

Huarong Huang,Qiuyan Zhang,Susan Goodin,Zhiyun Du,Kun Zhang,Dongli Li,Chelsea Farichon,Xi Zheng,Shaohua Chen,Jeremiah Van Doren,Yan He,Allan H Conney

doi:10.3892/mmr.2015.3238

Abstract

α-tomatine is a glycoalkaloid that occurs naturally in tomatoes (Lycopersicon esculentum). In the present study, the effects of α-tomatine on human myeloid leukemia HL-60 cells were investigated. Treatment of HL-60 cells with α-tomatine resulted in growth inhibition and apoptosis in a concentration-dependent manner. Tomatidine, the aglycone of tomatine had little effect on the growth and apoptosis of HL-60 cells. Growth inhibition and apoptosis induced by α-tomatine in HL-60 cells was partially abrogated by addition of cholesterol indicating that interactions between α-tomatine and cell membrane-associated cholesterol may be important in mediating the effect of α-tomatine. Activation of nuclear factor-κB by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate failed to prevent apoptosis in HL-60 cells treated with α-tomatine. In animal experiments, it was found that treatment of mice with α-tomatine inhibited the growth of HL-60 xenografts in vivo. Results from the present study indicated that α-tomatine may have useful anti-leukemia activities.

Highlights

The solanum‐steroid‐alkaloids found in plants of the Solanum species are of interest as a starting material for the synthesis of steroid hormones and exhibit notable pharmaceutical and toxicological properties [1,2]. α‐tomatine and tomatidineKey words: glycoalkaloid, α-tomatine, leukemia, apoptosis, growth inhibition, cholesterol (Fig. 1), occur naturally in tomatoes (Lycopersicon escul‐ entum), belonging to the group of solanum‐steroid‐alkaloids. α‐tomatine is a glycoalkaloid consisting of an aglycone moiety and a tetrasaccharide moiety (β‐lycotetraose), which is composed of two molecules of glucose, one galactose and one xylose; the four monosaccharides form a branched structure, which is attached at the C‐3 position of the aglycone (Fig. 1)
The effects and mechanisms of α‐tomatine were examined in HL‐60 human myeloid leukemia cells, which are widely used as a model system to investigate the effect of different anticancer agents [18,19]
The present study found that the addition of cholesterol significantly abrogated α‐tomatine‐induced growth inhibition and apoptosis in HL‐60 cells

Summary

Introduction

The solanum‐steroid‐alkaloids found in plants of the Solanum species are of interest as a starting material for the synthesis of steroid hormones and exhibit notable pharmaceutical and toxicological properties [1,2]. α‐tomatine and tomatidine. Previous studies have demonstrated that α‐tomatine has cytotoxic effects on insect and rat cells [9,10,11]. The anticancer effect of α‐tomatine has been investigated. Α‐tomatine inhibits the growth of lymphoma and leukemia cells [16,17]. The effects and mechanisms of α‐tomatine were examined in HL‐60 human myeloid leukemia cells, which are widely used as a model system to investigate the effect of different anticancer agents [18,19]. The present study found that α‐tomatine markedly inhibited growth and induced apoptosis in HL‐60 cells. Α‐tomatine inhibited the in vivo growth of HL‐60 cells in a mouse xenograft model The present study found that α‐tomatine markedly inhibited growth and induced apoptosis in HL‐60 cells. α‐tomatine inhibited the in vivo growth of HL‐60 cells in a mouse xenograft model

Methods

Results

Conclusion