Planta Med 2016; 82(05): 379-387
DOI: 10.1055/s-0042-100810
Mini Reviews
Georg Thieme Verlag KG Stuttgart · New York

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

Lenka Sucha
Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
,
Pavel Tomsik
Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
› Author Affiliations
Further Information

Publication History

received 13 January 2015
revised 08 December 2015

accepted 21 December 2015

Publication Date:
04 February 2016 (online)

Abstract

Steroidal glycoalkaloids present in Solanaceae are toxic compounds biosynthesised for the protection of the plants. However, many health benefits of these compounds have been reported so far. One of their promising targets might be cancer, as demonstrated in a large number of studies. However, the main mechanism of action seems to be unclear. It could include the induction of apoptosis or trigger a necrosis with a subsequent inflammatory response. The relatively high systemic toxicity of steroidal compounds is another effect that must be taken into account in anticancer research. The main aim of this work was to summarise the recent progress in the investigation of the mechanisms of their antitumour action and to discuss their potential.

 
  • References

  • 1 Mothes K, Schütte HR, Luckner M. Biochemistry of Alkaloids. Berlin: Wiley-VCH; 1985: 363
  • 2 Barceloux DG. Potatoes, tomatoes, and solanine toxicity (Solanum tuberosum L., Solanum lycopersicum L.). Dis Mon 2009; 55: 391-402
  • 3 Distl M, Wink M. Identification and quantification of steroidal alkaloids from wild tuber-bearing Solanum species by HPLC and LC-ESI-MS. Potato Res 2009; 52: 79-104
  • 4 Wink M. Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective. Phytochemistry 2003; 64: 3-19
  • 5 Wink M. Plant breeding: importance of plant secondary metabolites for protection against pathogens and herbivores. Theor Appl Genet 1988; 75: 225-233
  • 6 Knuthsen P, Jensen U, Schmidt B, Larsen IK. Glycoalkaloids in potatoes: content of glycoalkaloids in potatoes for consumption. J Food Compost Anal 2009; 22: 577-581
  • 7 Friedman M. Potato glycoalkaloids and metabolites: roles in the plant and in the diet. J Agric Food Chem 2006; 54: 8655-8681
  • 8 Knapp S, Bohs L, Nee M, Spooner DM. Solanaceae – a model for linking genomics with biodiversity. Comp Funct Genomics 2004; 5: 285-291
  • 9 Griffin WJ, Lin GD. Chemotaxonomy and geographical distribution of tropane alkaloids. Phytochemistry 2000; 63: 623-637
  • 10 van Gelder WM. Determination of the total C27-steroidal alkaloid composition of Solanum species by high-resolution gas chromatography. J Chromatogr A 1985; 331: 285-293
  • 11 Gregory P, Sinden SL, Osman SF, Tingey WM, Chessin DA. Glycoalkaloids of wild, tuber-bearing Solanum species. J Agric Food Chem 1981; 29: 1212-1215
  • 12 Osman SF, Herb SF, Fitzpatrick TJ, Schmiediche P. Glycoalkaloid composition of wild and cultivated tuber-bearing Solanum species of potential value in potato breeding programs. J Agric Food Chem 1978; 26: 1246-1248
  • 13 Blankemeyer JT, White JB, Stringer BK, Friedman M. Effect of α-tomatine and tomatidine on membrane potential of frog embryos and active transport of ions in frog skin. Food Chem Toxicol 1997; 35: 639-646
  • 14 Shih YW, Shieh JM, Wu PF, Lee YC, Chen YZ, Chiang TA. α-Tomatine inactivates PI3 K/Akt and ERK signaling pathways in human lung adenocarcinoma A549 cells: effect on metastasis. Food Chem Toxicol 2009; 47: 1985-1995
  • 15 Friedman M, Fitch TE, Yokoyama WE. Lowering of plasma LDL cholesterol in hamsters by the tomato glycoalkaloid tomatine. Food Chem Toxicol 2000; 38: 549-553
  • 16 Friedman M. Tomato glycoalkaloids: role in the plant and in the diet. J Agric Food Chem 2002; 50: 5751-5780
  • 17 Thorne HV, Clarke GF, Skuce R. The inactivation of herpes simplex virus by some Solanaceae glycoalkaloids. Antiviral Res 1985; 5: 335-343
  • 18 Sandrock RW, Vanetten HD. Fungal Sensitivity to and Enzymatic Degradation of the Phytoanticipin α-Tomatine. Phytopathology 1998; 88: 137-143
  • 19 Filderman RB, Kovacs BA. Anti-inflammatory activity of the steroid alkaloid glycoside, tomatine. Br J Pharmacol 1969; 37: 748-755
  • 20 Simons V, Morrissey JP, Latijnhouwers M, Csukai M, Cleaver A, Yarrow C, Osbourn A. Dual effects of plant steroidal alkaloids on Saccharomyces cerevisiae . Antimicrob Agents Chemother 2006; 50: 2732-2740
  • 21 Irving jr. GW, Fontaine TD, Doolittle SP. Partial antibiotic spectrum of tomatine, an antibiotic agent from the tomato plant. J Bacteriol 1946; 52: 601-607
  • 22 Morrow WJ, Yang YW, Sheikh NA. Immunobiology of the tomatine adjuvant. Vaccine 2004; 22: 2380-2384
  • 23 Roddick JG. The acetylcholinesterase-inhibitory activity of steroidal glycoalkaloids and their aglycones. Phytochemistry 1989; 28: 2631-2634
  • 24 Friedman M, Fitch TE, Levin CE, Yokoyama WH. Feeding tomatoes to hamsters reduces their plasma low-density lipoprotein cholesterol and triglycerides. J Food Sci 2000; 65: 897-900
  • 25 Cayen MN. Effect of dietary tomatine on cholesterol metabolism in the rat. J Lipid Res 1971; 12: 482-490
  • 26 Roddick JG, Drysdale RB. Destabilization of liposome membranes by the steroidal glycoalkaloid α-tomatine. Phytochemistry 1984; 23: 543-547
  • 27 Machado RMD, Toledo MCF, Garcia LC. Effect of light and temperature on the formation of glycoalkaloids in potato tubers. Food Control 2007; 18: 503-508
  • 28 Friedman M, Dao L. Distribution of glycoalkaloids in potato plants and commercial potato. J Agric Food Chem 1992; 40: 419-423
  • 29 Haddadin MSY, Humeid MA, Qaroot FA, Robinson RK. Effect of exposure to light on the solanine content of two varieties of potato (Solanum tuberosum) popular in Jordan. Food Chem 2001; 73: 205-208
  • 30 Langkilde S, Mandimika T, Schrøder M, Meyer O, Slob W, Peijnenburg A, Poulsen M. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, α-solanine and α-chaconine in the Syrian Golden hamster. Food Chem Toxicol 2009; 47: 1099-1108
  • 31 Blankemeyer JT, McWilliams ML, Rayburn JR, Weissenberg M, Friedman M. Developmental toxicology of solamargine and solasonine glycoalkaloids in frog embryos. Food Chem Toxicol 1998; 36: 383-389
  • 32 Esteves-Souza A, Sarmento da Silva TM, Alves CC, de Carvalho MG, Braz-Filho B, Echevarria A. α-Solasonine from S. crinitum and S. jabrense was cytotoxic against Ehrlich carcinoma and human K562 leukemia cells. J Braz Chem Soc 2002; 13: 838-842
  • 33 Ding X, Zhu F, Yang Y, Li M. Purification, antitumor activity in vitro of steroidal glycoalkaloids from black nightshade (Solanum nigrum L.). Food Chem 2013; 141: 1181-1186
  • 34 Koduru S, Grierson DS, Van de Venter M, Afolayan AJ. Anticancer activity of steroid alkaloids isolated from Solanum aculeastrum . Pharm Biol 2007; 45: 613-618
  • 35 Bhattacharya S, Kohli S, Chaudhary AS. Isolation of solasodine from the unripe fruits of Solanum xanthocarpum Schrad and Wendl. (Solanaceae) and itʼs anti cancer activity against HeLa and U937 cell lines. Austral-Asian J Cancer 2013; 12: 199-213
  • 36 Fazil P, Ali RA. Isolation of a new steroidal glycoalkaloid from Solanum xanthocarpum . J Basic Appl Sci 2014; 10: 28-32
  • 37 Xie X, Zhu H, Yang H, Huang W, Wu Y, Wang Y, Luo Y, Wang D, Shao G. Solamargine triggers hepatoma cell death through apoptosis. Oncol Lett 2015; 10: 168-174
  • 38 Shiu LY, Liang CH, Chang LC, Sheu HM, Tsai EM, Kuo KW. Solamargine induces apoptosis and enhances susceptibility to trastuzumab and epirubicin in breast cancer cells with low or high expression levels of HER2/neu. Biosci Rep 2009; 29: 35-45
  • 39 Hu K, Kobayashi H, Dong A, Jing Y, Iwasaki S, Yao X. Antineoplastic agents. III: Steroidal glycosides from Solanum nigrum . Planta Med 1999; 65: 35-38
  • 40 Weissenberg M, Levy A, Svoboda JA, Ishaaya I. The effect of some Solanum steroidal alkaloids and glycoalkaloids on larvae of the red flour beetle, Tribolium castaneum, and the tobacco hornworm, Manduca sexta . Phytochemistry 1998; 47: 203-209
  • 41 Chataing B, Concepción JL, Lobatón R, Usubillaga A. Inhibition of Trypanosoma cruzi growth in vitro by Solanum alkaloids: a comparison with ketoconazole. Planta Med 1998; 64: 31-36
  • 42 Roddick JG, Weissenberg M, Leonard AL. Membrane disruption and enzyme inhibition by naturally-occurring and modified chacotriose-containing Solanum steroidal glycoalkaloids. Phytochemistry 2001; 56: 603-610
  • 43 Bushway RJ, Savage SA, Ferguson BS. Inhibition of acetyl cholinesterase by solanaceous glycoalkaloids and alkaloids. Am J Potato Res 1987; 64: 409-413
  • 44 Wilson RH, Poley GW, De Eds F. Some pharmacologic and toxicologic properties of tomatine and its derivatives. Toxicol Appl Pharmacol 1961; 3: 39-48
  • 45 Roddick JG. The steroidal glycoalkaloid α-tomatine. Phytochemistry 1974; 13: 9-25
  • 46 Mensinga TT, Sips AJ, Rompelberg CJ, van Twillert K, Meulenbelt J, van den Top HJ, van Egmond HP. Potato glycoalkaloids and adverse effect in humans: an ascending dose study. Regul Toxicol Pharmacol 2005; 41: 66-72
  • 47 Patil BC, Sharma RP, Salunkhe DK, Salunkhe K. Evaluation of solanine toxicity. Food Cosmet Toxicol 1972; 10: 395-398
  • 48 Bell DP, Gibson JG, McCarroll AM, McClean GA. Embryotoxicity of solanine and aspirin in mice. J Reprod Fertil 1976; 46: 257-259
  • 49 Rayburn JR, Friedman M, Bantle JA. Synergistic interaction of glycoalkaloids α-chaconine and α-solanine on developmental toxicity in Xenopus embryos. Food Chem Toxicol 1995; 33: 1013-1019
  • 50 Korpan YI, Nazarenko EA, Skryshevskaya IV, Martelet C, Jaffrezic-Renault N, Elʼskaya AV. Potato glycoalkaloids: true safety or false sense of security?. Trends Biotechnol 2004; 22: 147-151
  • 51 Nishie K, Norred WP, Swain AP. Pharmacology and toxicology of chaconine and tomatine. Res Commun Chem Pathol Pharmacol 1975; 12: 657-668
  • 52 Almeida AE, Cardoso CRP, Almeida DV, Moreira RRD, Silva M, Varanda EA. Mutagenic activity of glycoalkaloids from Solanum palinacanthum Dunal (Solanaceae) found in the Brazilian cerrado. Lat Am J Pharm 2010; 29: 122-126
  • 53 Zheng X, Xu L, Liang Y, Xiao W, Xie L, Zhang Y, Zhao L, Cao L, Chen J, Wang G. Quantitative determination and pharmacokinetic study of solamargine in rat plasma by liquid chromatogramy-mass spectrometry. J Pharm Biomed Anal 2011; 55: 1157-1162
  • 54 Francis G, Kerem Z, Makkar HP, Becker K. The biological action of saponins in animal systems: a review. Br J Nutr 2002; 88: 587-605
  • 55 Keukens EA, de Vrije T, Fabrie CH, Demel RA, Jongen WM, de Kruijff B. Dual specifity of sterol-mediated glycoalkaloid induced membrane disruption. Biochim Biophys Acta 1992; 1110: 127-136
  • 56 Roddick JG. Complex formation between solanaceous steroidal glycoalkaloids and free sterols in vitro . Phytochemistry 1979; 18: 1467-1470
  • 57 Caldwell KA, Grosjean OK, Henika PR, Friedman M. Hepatic ornithine decarboxylase induction by potato glycoalkaloids in rats. Food Chem Toxicol 1991; 29: 531-535
  • 58 Lee KR, Kozukue N, Han JS, Park JH, Chang EY, Baek EJ, Chang JS, Friedman M. Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells. J Agric Food Chem 2004; 52: 2832-2839
  • 59 Smith DB, Roddick JG, Jones JL. Potato glycoalkaloids: some unanswered questions. Trends Food Sci Tech 1996; 7: 126-131
  • 60 Friedman M, Levin CE, Lee SU, Kim HJ, Lee IS, Byun JO, Kozukue N. Tomatine-containing green tomato exctracts inhibic growth of human breast, colon, liver, and stomach cancer cells. J Agric Food Chem 2009; 57: 5727-5733
  • 61 Shieh JM, Cheng TH, Shi MD, Wu PF, Chen Y, Ko SC, Shih YW. α-Tomatine suppresses invasion and migration of human non-small cell lung cancer NCI-H460 cells through inactivating FAK/PI3 K/Akt signaling pathway and reducing binding activity of NF-κB. Cell Biochem Biophys 2011; 60: 279-310
  • 62 Lee ST, Wong PF, Cheah SC, Mustafa MR. Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells. PLoS One 2011; 6: e18915
  • 63 Lee ST, Wong PF, Hooper JD, Mustafa MR. Alpha-tomatine synergises with paclitaxel to enhance apoptosis of androgen-independent human prostate cancer PC-3 cells in vitro and in vivo . Phytomedicine 2013; 20: 1297-1305
  • 64 Shi MD, Shih YW, Lee YS, Cheng YF, Tsai LY. Suppression of 12-O-tetradecanoylphorbol-13-acetate-induced MCF-7 breast adenocarcinoma cells invasion/migration by α-tomatine through activation PKCα/ERK/NF-κB-dependent MMP-2/MMP-9 expressions. Cell Biochem Biophys 2012; 66: 161-174
  • 65 Sucha L, Hroch M, Rezacova M, Rudolf E, Havelek R, Sispera L, Cmielova J, Kohlerova R, Bezrouk A, Tomsik P. The cytotoxic effect of α-tomatine in MCF-7 human adenocarcinoma breast cancer cells depends on its interaction with cholesterol in incubation media and does not involve apoptosis induction. Oncol Rep 2013; 30: 2593-2602
  • 66 Kúdelová J, Seifrtová M, Suchá L, Tomšík P, Havelek R, Řezáčová M. Alpha-tomatine activates cell cycle checkpoints in the absence of DNA damage in human leukemic MOLT-4 cells. J Appl Biomed 2013; 11: 93-103
  • 67 Chao MW, Chen CH, Chang YL, Teng CM, Pan SL. α-Tomatine-mediated anti-cancer activity in vitro and in vivo through cell cycle- and caspase-independent pathways. PLoS One 2012; 7: e44093
  • 68 Friedman M, McQuistan T, Hendricks JD, Pereira C, Balley GS. Protective effect of dietary tomatine against dibenzo[a,l]pyrene(DBP)-induced liver and stomach tumors in rainbow trout. Mol Nutr Food Res 2007; 51: 1485-1491
  • 69 Lee ST, Wong PF, He H, Hooper JD, Mustafa MR. Alpha-tomatine attenuation of in vivo growth of subcutaneous and orthotopic xenograft tumors of human prostate carcinoma PC-3 cells is accompanied by inactivation of nuclear factor-kappa B signaling. PLoS One 2013; 8: e57708
  • 70 Tomsik P, Micuda S, Sucha L, Cermakova E, Suba P, Zivny P, Mazurova Y, Knizek J, Niang M, Rezacova M. The anticancer activity of alpha-tomatine against mammary adenocarcinoma in mice. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013; 157: 153-161
  • 71 Lu MK, Shih YW, Chang Chien TT, Fang LH, Huang HC, Chen PS. α-Solanine inhibits human melanoma cell migration and invasion by reducing matrix metalloproteinase-2/9 activities. Biol Pharm Bull 2010; 33: 1685-1691
  • 72 Ji YB, Gao SY, Ji CF, Zou X. Induction of apoptosis in HepG2 cells by solanine and Bcl-2 protein. J Ethnopharmacol 2008; 115: 194-202
  • 73 Gao SY, Wang QJ, Ji YB. Effect of solanine on the membrane potential of mitochondria in HepG2 cells and [Ca2+] in the cells. World J Gastroenterol 2006; 12: 3359-3367
  • 74 Friedman M, Lee KR, Kim HJ, Lee IS, Kozukue N. Anticarcinogenic effects of glycoalkaloids from potatoes against human cervical, liver, lymphoma, and stomach cancer cells. J Agric Food Chem 2005; 53: 6162-6169
  • 75 Yamashoji S, Matsuda T. Synergistic cytotoxicity induced by α-solanine and α-chaconine. Food Chem 2013; 141: 669-674
  • 76 Mohsenikia M, Alizadeh AM, Khodayari S, Kodayari H, Kouhpayeh SA, Karimi A, Zamani M, Azizian S, Mohagheghi MA. The protective and therapeutic effects of alpha-solanine on mice breast cancer. Eur J Pharmacol 2013; 718: 1-9
  • 77 Lv C, Kong H, Dong G, Liu L, Tong K, Sun H, Chen B, Zhang C, Zhou M. Antitumor efficacy of α-solanine against pancreatic cancer in vitro and in vivo . PLoS One 2014; 9: e87868
  • 78 Sun H, Lv C, Yang L, Wang Y, Zhang Q, Yu S, Kong H, Wang M, Xie J, Zhang C, Zhou M. Solanine induces mitochondria-mediated apoptosis in human pancreatic cancer cells. Biomed Res Int 2014; 2014: 805926
  • 79 Esteves-Souza A, Sarmento da Silva TM, Alves CCF, de Carvalho MG, Braz-Filho R, Echevarria A. Cytotoxic activities against Ehrlich carcinoma and human K562 leukemia of alkaloids and flavonoid from two Solanum species. J Brazil Chem Soc 2002; 13: 838-842
  • 80 Munari CC, de Oliveira PF, Campos JC, Martins Sde P, Da Costa JC, Bastos JK, Tavares DC. Antiproliferative activity of Solanum lycocarpum alkaloidic extract and their constituents, solamargine and solasonine, in tumor cell lines. J Nat Med 2014; 68: 236-241
  • 81 Sun L, Zhao Y, Li X, Yuan H, Cheng A, Lou H. A lysosomal-mitochondrial death pathway is induced by solamargine in human K562 leukemia cells. Toxicol In Vitro 2010; 24: 1504-1511
  • 82 Sun L, Zhao Y, Yuan H, Li X, Cheng A, Lou H. Solamargine, a steroidal alkaloid glycoside, induces oncosis in human K562 leukemia and squamous cell carcinoma KB cells. Cancer Chemother Pharmacol 2011; 67: 813-821
  • 83 Hsu SH, Tsai TR, Lin CN, Yen MH, Kuo KW. Solamargine purified from Solanum incanum Chinese herb triggers gene expression of human TNFR I which may lead to cell apoptosis. Biochem Biophys Res Commun 1996; 229: 1-5
  • 84 Chang LC, Tsai TR, Wang JJ, Lin CN, Kuo KW. The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis. Biochem Biophys Res Commun 1998; 242: 21-25
  • 85 Kuo KW, Hsu SH, Li YP, Lin WL, Liu LF, Chang LC, Lin CC, Sheu HM. Anticancer activity evaluation of the Solanum glycoalkaloid solamargine. Triggering apoptosis in human hepatoma cells. Biochem Pharmacol 2000; 60: 1865-1873
  • 86 Ding X, Zhu FS, Li M, Gao SG. Induction of apoptosis in human hepatoma SMMC-7721 cells by solamargine from Solanum nigrum L. J Ethnopharmacol 2012; 139: 599-604
  • 87 Liu LF, Liang CH, Shiu LY, Lin WL, Lin CC, Kuo KW. Action of solamargine on human lung cancer cells – enhancement of the susceptibility of cancer cells to TNFs. FEBS Lett 2004; 577: 67-74
  • 88 Shiu LY, Chang LC, Liang CH, Huang YS, Sheu HM, Kuo KW. Solamargine induces apoptosis and sensitizes breast cancer cells to cisplatin. Food Chem Toxicol 2007; 45: 2155-2164
  • 89 Shiu LY, Liang CH, Huang YS, Sheu HM, Kuo KW. Downregulation of HER2/neu receptor by solamargine enhances anticancer drug-mediated cytotoxicity in breast cancer cells with high-expressing HER2/neu. Cell Biol Toxicol 2008; 24: 1-10
  • 90 Zhou Y, Tang Q, Zhao S, Zhang F, Li L, Wu W, Wang Z, Hann S. Targeting signal transducer and activator of transcription 3 contributes to the solamargine-inhibited growth and -induced apoptosis of human lung cancer cells. Tumour Biol 2014; 35: 8169-8178
  • 91 Li X, Zhao Y, Wu WK, Liu S, Cui M, Lou H. Solamargine induces apoptosis associated with p 53 transcription-dependent and transcription-independent pathways in human osteosarcoma U2OS cells. Life Sci 2011; 88: 314-321
  • 92 Liang CH, Liu LF, Shiu LY, Huang YS, Chang LC, Kuo KW. Action of solamargine on TNFs and cisplatin-resistant human lung cancer cells. Biochem Biophys Res Commun 2004; 322: 751-758
  • 93 Li X, Zhao Y, Ji M, Liu SS, Cui M, Lou HX. Induction of actin disruption and downregulation of P-glycoprotein expression by solamargine in multidrug-resistant K562/A02 cells. Chin Med J 2011; 124: 2038-2044
  • 94 Cham BE. Drug therapy: Solamargine and other solasodine rhamnosyl glycosides as anticancer agents. Modern Chemotherapy 2013; 2: 33-49
  • 95 Cham BE. Topical solasodine rhamnosyl glycosides derived from the eggplant treats large skin cancers: two case reports. Int J Clin Med 2011; 2: 473-477
  • 96 Punjabi S, Cook LJ, Kersey P, Marks R, Cerio R. Solasodine glycoalkaloids: a novel topical therapy for basal cell carcinoma. A double-blind, randomized, placebo-controlled, parallel group, multicenter study. Int J Dermatol 2008; 47: 78-82
  • 97 Van der Most RG, Himbeck R, Aaron S, Carter SJ, Larma I, Robinson C, Currie A, Lake RA. Antitumor efficacy of the novel chemotherapeutic agent coramsine is potentiated by cotreatment with CpG-containing oligodeoxynucleotides. J Immunother 2006; 29: 134-142
  • 98 Millward M, Powell A, Tyson S, Daly P, Ferguson R, Carter S. Phase I trial of coramsine (SBP002) in patients with advanced solid tumors. J Clin Oncol 2005; 23: 3105
  • 99 Badami S, Manohara Reddy SA, Kumar EP, Vijayan P, Suresh B. Antitumor activity of total alkaloid fraction of Solanum pseudocapsicum leaves. Phytother Res 2003; 17: 1001-1004
  • 100 Vijayan P, Vijayaraj P, Setty PH, Hariharpura RC, Godavarthi A, Badami S, Arumugam DS, Bhojraj S. The cytotoxic activity of the total alkaloids isolated from different parts of Solanum pseudocapsicum . Pharm Bull 2004; 27: 528-530
  • 101 Kupchan SM, Barboutis SJ, Knox JR, Cam CA. Beta-solamarine: tumor inhibitor isolated from Solanum dulcamara . Science 1965; 150: 1827-1828
  • 102 Al-Rehailya AJ, Ahmada MS, Mustafaa J, Al-Oqaila MM, Hassana WH, Khanb SI, Khana IA. Solanopubamine, a rare steroidal alkaloid from Solanum schimperianum: Synthesis of some new alkyl and acyl derivatives, their anticancer and antimicrobial evaluation. J Saudi Chem Soc 2013; 17: 67-76
  • 103 Iijiama Y, Watanabe B, Sasaki R, Takenaka M, Ono H, Sakurai N, Umemoto N, Suzuki H, Shibata D, Aoki K. Steroidal glycoalkaloid profiling and structures of glycoalkaloids in wild tomato fruit. Phytochemistry 2013; 95: 145-157
  • 104 Chiu FL, Lin JK. Tomatidine inhibits iNOS and COX-2 through suppression of NF-kappaB and JNK pathways in LPS-stimulated mouse macrophages. FEBS Lett 2008; 582: 207-212
  • 105 Yan KH, Lee LM, Yan SH, Huang HC, Li CC, Lin HT, Chen PS. Tomatidine inhibits invasion of human lung adenocarcinoma cell A549 by reducing matrix metalloproteinases expression. Chem Biol Interact 2013; 203: 580-587
  • 106 Yang YW, Wu CA, Morrow WJ. The apoptotic and necrotic effects of tomatine adjuvant. Vaccine 2004; 22: 2316-2327
  • 107 Cham BE, Chase TR. Solasodine rhamnosyl glycosides cause apoptosis in cancer cells. Do they also prime the immune system resulting in long-term protection against cancer?. Planta Med 2012; 78: 349-353
  • 108 Ledoux S, Yang R, Friedlander G, Laouari D. Glucose depletion enhances P-glycoprotein expression in hepatoma cells: role of endoplasmatic reticulum stress response. Cancer Res 2003; 63: 7284-7290
  • 109 Loo TW, Clarke DM. Merck Frosst Award Lecture 1998. Molecular dissection of the human multidrug resistance P-glycoprotein. Biochem Cell Biol 1999; 77: 11-23
  • 110 Lavie Y, Harel-Orbital T, Gaffield W, Liscovitch M. Inhibitory effect of steroidal alkaloids on drug transport and multidrug resistance in human cancer cells. Anticancer Res 2001; 21: 1189-1194
  • 111 Yang SA, Paek SH, Kozukue N, Lee KR, Kim JA. α-Chaconine, a potato glycoalkaloid, induces apoptosis of HT-29 human colon cancer cells through caspase-3 activation and inhibition of ERK 1/2 phosphorylation. Food Chem Toxicol 2006; 44: 839-846
  • 112 Lu MK, Chen PH, Shih YW, Chang YT, Huang ET, Liu CR, Chen PS. α-Chaconine inhibits angiogenesis in vitro by reducing matrix metalloproteinase-2. Biol Pharm Bull 2010; 33: 622-630
  • 113 Liang CH, Shiu LY, Chang LC, Sheu HM, Kuo KW. Solamargine upregulation of Fas, downregulation of HER2, and enhancement of cytotoxicity using epirubicin in NSCLC cells. Mol Nutr Food Res 2007; 51: 999-1005
  • 114 Schmitz I, Kirchhoff S, Krammer PH. Regulation of death receptor-mediated apoptosis pathways. Int J Biochem Cell Biol 2000; 32: 1123-1136
  • 115 de Bruin EC, Medema JP. Apoptosis and non-apoptotic deaths in cancer development and treatment response. Cancer Treat Rev 2008; 34: 737-749
  • 116 Podolak I, Galanty A, Sobolewska D. Saponins as cytotoxic agents: a review. Phytochem Rev 2010; 9: 425-474
  • 117 Keukens EA, de Vrije T, Jansen LA, de Boer H, Janssen M, de Kroon AI, Jongen WM, de Kruijff B. Glycoalkaloids selectively permeabilize cholesterol containing biomembranes. Biochim Biophys Acta 1996; 1279: 243-250
  • 118 Toyoda M, Rausch WD, Inoue K, Ohno Y, Fujiyama Y, Takagi K, Saito Y. Comparison of solanaceous glycoalklaoids-evoked Ca2+ influx in different types of cultured cells. Toxicol In Vitro 1991; 5: 347-351
  • 119 Roddick JG, Rijnenberg AL, Osman SF. Synergistic interaction between potato glycoalkaloids α-solanine and α-chaconine in relation to destabilization of cell membranes: Ecological implications. J Chem Ecol 1988; 14: 889-902
  • 120 Nishie K, Gumbmann MR, Keyl AC. Pharmacology of solanine. Toxicol Appl Pharmacol 1971; 19: 81-92
  • 121 Al Chami L, Méndez R, Chataing B, OʼCallaghan J, Usubillaga A, LaCruz L. Toxicological effects of α-solamargine in experimental animals. Phytother Res 2003; 17: 254-258