The anticancer activity of alpha-tomatine against mammary adenocarcinoma in mice

Abstract

Aim. To evaluate the anticancer effect of alpha-tomatine (i.p.) either alone or in combination with doxorubicin (i.v.) in a mouse tumour model. Methods. We studied the effect of repeated alpha-tomatine (0.1 -9 mg/kg) and/or doxorubicin (2 mg/kg) on the growth and mitotic activity of the solid Ehrlich tumour in vivo, as well as on the survival of the tumour-bearing mice. Results. Monotherapy with alpha-tomatine had a significant dose-dependent anticancer effect which peaked at 1 mg/kg. This was shown by both slowed tumour growth and reduced tumour cell proliferation. We also provide the first evidence that the combination alpha-tomatine (1 mg/kg) and doxorubicin (2 mg/kg) had a synergistic effect and significantly prolonged the survival of the mice. Neither alpha-tomatine nor doxorubicin influenced the infiltration of tumours with CD3+ lymphocytes; nor were we able to find an in vivo modulation of the key molecules of two regulatory pathways reported in vitro as the principal anti-cancer mechanisms of alpha-tomatine, i.e. iNOS and phosphorylated ERK2. However, alpha-tomatine still led to intracellular DNA inhibition and protein synthesis in Ehrlich tumour cells in a short-term culture ex vivo with IC 50 values of 8.7 and 6.6 µM. Conclusions.The results suggest that ΤΟΜ, especially in combination with doxorubicin, may be a promising agent for the treatment of malignant solid tumours. Despite growing knowledge of the mechanisms of ΤΟΜ action in cancer cells, most aspects remain unclear. Parallel organ toxicity, especially potential liver effects, requires careful attention when performing in vivo studies in the future.

The Steroidal Glycoalkaloids from Solanaceae: Toxic Effect, Antitumour Activity and Mechanism of Action

“…In addition, it inhibited the human prostate carcinoma PC-3 xenograft alone as well as tumour growth in severe combined immunodeficient mice in combination therapy with paclitaxel [63,69]. Tomsik et al demonstrated the inhibition of solid Ehrlich tumour growth in mice after α-tomatine treatment, augmented by combination therapy with doxorubicin [70].…”

“…Importantly, the cytotoxic effect of α-tomatine is related to its binding to cholesterol, which causes the disruption of cell membranes and cell necrosis [65]. The in vivo results [70] suggest that α-tomatine might stimulate anticancer immune surveillance. This is in accordance with previous findings on its immunomodulatory effect (see above).…”

Secondary Metabolites in Medicinal and Aromatic Plants (MAPs): Potent Molecules in Nature’s Arsenal to Fight Human Diseases

“…Cocaine (Erythroxylaceae genera such as Conium maculatum, Sarracenia flava) are neurotoxins (Hajek et al 2013;Panter et al 2013), and vinblastine, vinorelbine, vincristine, and vindesine (Apocynaceae genera such as Catharanthus roseus G.) have antitumor and antidiabetic effects and lower high blood pressure (Jordan and Leslie 2004;Moudi et al 2013). The reserpine lowers high blood pressure (Reyburn et al 2009); tomatine (Solanum lycopersicum) has anticancer, antifungal, and immune effects (Gao and Hu 2010;Morrow et al 2004;Tomsik et al 2013); and strychnine (Strychnos nux-vomica) has anticonvulsant and pesticide effects (Dopham et al 2014;Jensen et al 2006;Umukoro et al 2013). The cytisine (Cytisus laburnum) acts as acetylcholine agonist (Porreca et al 1983;West et al 2011).…”

Combination of α-Tomatine and Curcumin Inhibits Growth and Induces Apoptosis in Human Prostate Cancer Cells

“…In vitro studies demonstrated that α-tomatine inhibited the growth of different human cancer cells [ 23 – 25 ]. Recent studies also showed that α-tomatine inhibited the growth of mammary and prostate tumors in mice [ 26 , 27 ]. A combination of α-tomatine and paclitaxel was found to synergistically enhance apoptosis of human prostate cancer cells [ 28 ].…”