Saponins as cytotoxic agents: A review

Phytochemistry Reviews

Volumn 9, Issue 3, 2010, Pages 425-474

  Podolak, Irma ^a   Galanty, Agnieszka ^a   Sobolewska, Danuta ^a  

^a JAGIELLONIAN UNIVERSITY   (Poland)

Author keywords

Cytotoxic mechanisms; Glycosides; Sar; Steroid; Triterpenoid

Indexed keywords

ALBIZOSIDE A; ALBIZOSIDE C; ALBIZOSIDE DERIVATIVE; CORIARIOSIDE A; CYTOTOXIC AGENT; DACTINOMYCIN; DASYSCYPHIN C; DURANTANIN IV; DURANTANIN V; FATSIASIDE C1; FRONDOSIDE A; GIGANTEOSIDE D; GIGANTEOSIDE E; GINSENOSIDE RK1; GLOCHIERIOSIDE A; GLOCHIERIOSIDE B; GORDONOSIDE C; GORDONOSIDE DERIVATIVE; GUAIANIN N; GUMMIFERAOSIDE A; GUMMIFERAOSIDE B; GUMMIFERAOSIDE C; JULIBROSIDE J21; MITOXANTRONE; SAPONIN DERIVATIVE; SAPONOSIDE; SYNAPTOSIDE A; TRITERPENE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINBLASTINE;

ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; BREAST CANCER; COLON CANCER; CONCENTRATION RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG HALF LIFE; DRUG ISOLATION; DRUG MECHANISM; DRUG METABOLISM; HUMAN; IC 50; LEUKEMIA; LUNG ADENOCARCINOMA; MALIGNANT NEOPLASTIC DISEASE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; REVIEW; STRUCTURE ACTIVITY RELATION;

EID: 77956339773     PISSN: 15687767     EISSN: 1572980X     Source Type: Journal    
DOI: 10.1007/s11101-010-9183-z     Document Type: Review

References (150)

1. H Abe H Konishi H Komiya, et al. 1981 Effects of saikosaponins on biological membranes Planta Med 42 356 363
2. D Acharya A-C Mitaine-Offer N Kaushik, et al. 2009 Cytotoxic spirostane-type saponins from the roots of Chlorophytum borivilianum J Nat Prod 72 177 181 19128156
3. WS Ahmed MA Mohamed RA El-Dib, et al. 2009 New triterpene saponins from Duranta repens Linn. and their cytotoxic activity Molecules 14 1952 1965 19471216
4. SA Avilov AS Silchenko AS Antonov, et al. 2008 Synaptosides A and A1, triterpene glycosides from the sea cucumber Synapta maculata containing 3-O-methylglucuronic acid and their cytotoxic activity against tumor cells J Nat Prod 71 525 531 18290630
5. C Bachran M Sutherland I Heisler, et al. 2006 The saponin-mediated enhanced uptake of targeted saporin-based drugs is strongly dependent on the saponin structure Exp Biol Med 231 412 420
6. C Bachran S Bachran M Sutherland, et al. 2008 Saponins in tumor therapy Mini Rev Med Chem 8 575 584 18537712
7. C Bachran H Durkop M Sutherland, et al. 2009 Inhibition of tumor growth by targeted toxins in mice is dramatically improved by saponinum album in a synergistic way J Immunother 32 713 725 19561537
8. C Bachran A Weng D Bachran, et al. 2010 The distribution of saponins in vivo affects their synergy with chimeric toxins against tumours expressing human epidermal growth factor receptors in mice Br J Pharmacol 159 345 352 20015087
9. S-C Bang J-H Lee G-Y Song, et al. 2005 Antitumor activity of Pulsatilla koreana saponins and their structure-activity relationship Chem Pharm Bull 53 11 1451 1454 16272730
10. S-C Bang H-H Seo H-Y Yun, et al. 2007 Facile synthesis of trisaccharide moiety corresponding to antitumor activity in triterpenoid saponins isolated from Pulsatilla roots Chem Pharm Bull 55 1734 1739 18057749
11. W Bao H Pan M Lu, et al. 2007 The apoptotic effect of sarsasapogenin from Anemarrhena asphodeloides on HepG2 human hepatoma cells Cell Biol Int 31 887 892 17400003
12. G Blunden MC Culling K Jewers 1975 Steroidal sapogenins: a review of actual and potential plant sources Trop Sci 17 139 154
13. Bruneton J (1995) Pharmacognosie, Phytochimie, Plantes Médicinales; Éditions Technique & Documentation, Paris, p 1120
14. LM Calabria S Piacente I Kapusta, et al. 2008 Triterpene saponins from Silphium radula Phytochemistry 69 961 972 18039545
15. S Cao A Norris JS Miller, et al. 2007 Cytotoxic triterpenoid saponins of Albizia gummifera from the Madagascar rain forest J Nat Prod 70 361 366 17263578
16. BE Cham B Daunter 1990 Solasodine glycosides. Selective cytotoxicity for cancer cells and inhibition of cytotoxicity by rhamnose in mice with sarcoma 180 Cancer Lett 55 221 225 2257540
17. P-K Chan 2007 Acylation with diangeloyl groups at C21-22 positions in triterpenoid saponins is essential for cytotoxicity towards tumor cells Biochem Pharmacol 73 341 350 17092489
18. P-K Chan M Zhao C-T Che, et al. 2008 Cytotoxic acylated triterpene saponins from the husks of Xanthoceras sorbifolia J Nat Prod 71 1247 1250 18549275
19. L-C Chang T-R Tsai J-J Wang, et al. 1998 The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis Biochem Biophys Res Commun 242 21 25 9439603
20. X Chang W Li Z Jia, et al. 2007 Biologically active triterpenoid saponins from Ardisia japonica J Nat Prod 70 179 187 17243725
21. HF Chen GH Wang Q Luo, et al. 2009 Two new steroidal saponins from Allium macrostemon Bunge and their cytotoxity on different cancer cell lines Molecules 14 6 2246 2253 19553896
22. M Chwalek K Plé L Voutquenne-Nazabadioko 2004 Synthesis and hemolytic activity of some hederagenin diglycosides Chem Pharm Bull 52 965 971 15304991
23. M Chwalek N Lalun H Bobichon, et al. 2006 Structure-activity relationships of some hederagenin diglycosides: haemolysis, cytotoxicity and apoptosis induction Biochim Biophys Acta 1760 1418 1427 16875785
24. P Cmoch Z Pakulski J Swaczynova, et al. 2008 Synthesis of lupane-type saponins bearing mannosyl and 3,6-branched trimannosyl residues and their evaluation as anticancer agents Carbohydrate Res 343 995 1003
25. SH Dongre S Badami G Ashok, et al. 2007 In vitro cytotoxic properties of O-methylsolanocapsine isolated from Solanum pseudocapsicum leaves Indian J Pharmacol 39 4 208 209
26. LS Einbond Y Wen-Cai K He, et al. 2008 Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells Phytomedicine 15 504 511 17980565
27. A Ellington M Berhow KW Singletary 2005 Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins Carcinogenesis 26 159 167 15471899
28. C Fiore M Eisenhut E Ragazzi, et al. 2005 A history of the therapeutic use of liquorice in Europe J Ethnopharmacol 99 317 324 15978760
29. G Francis Z Kerem HPS Makkar, et al. 2002 The biological action of saponins in animal systems: a review Br J Nutr 88 587 605 12493081
30. H Fuchs D Bachran H Panijdeh, et al. 2009 Saponins as tool for improved targeted tumor therapies Curr Drug Targets 10 140 151 19199910
31. A Galanty M Michalik Ł Sȩdek, et al. 2008 The influence of LTS-4, a saponoside from Lysimachia thyrsiflora L., on human skin fibroblasts and human melanoma cells Cell Mol Biol Lett 13 585 598 18553182
32. C Gauthier J Legault M Lebrun, et al. 2006 Glycosidation of lupane-type triterpenoids as potent in vitro cytotoxic agents Bioorg Med Chem 14 6713 6725 16787747
33. C Gauthier J Legault K Girard-Lalancette, et al. 2009 Haemolytic activity, cytotoxicity and membrane cell permeabilization of semi-synthetic and natural lupane- and oleanane-type saponins Bioorg Med Chem 17 2002 2008 19200744
34. C Gauthier J Legault A Pichette 2009 Recent progress in the synthesis of naturally ocurring triterpenoid saponins Mini-Rev Org Chem 6 321 344
35. C Gnoula V Megalizzi N De Neve, et al. 2008 Balanitin-6 and -7: diosgenyl saponins isolated from Balanites aegyptiaca Del. display significant anti-tumor activity in vitro and in vivo Int J Oncol 32 5 15 18097538
36. 2 and its pharmacokinetic application in dogs: a case for the influence of micronization on traditional Chinese medicine Int J Mass Spectrom 252 11 19
37. Ö Güçlü-Üstündaǧ G Mazza 2007 Saponins: properties, applications and processing Crit Rev Food Sci Nutr 47 231 258 17453922
38. AI Hamed S Piacente G Autore, et al. 2005 Antiproliferative hopane and oleanane glycosides from the roots of Glinus lotoides Planta Med 71 554 560 15971128
39. K Haralampidis M Trojanowska AE Osbourn 2002 Biosynthesis of triterpenoid saponins in plants Adv Biochem Eng/Biotechnol 75 31 48
40. V Haridas G Nishimura Z-X Xu, et al. 2009 Avicin D: a protein reactive plant isoprenoid dephosphorylates Stat 3 by regulating both kinase and phosphatase activities PloS ONE 5 1 13
41. X He A Qiao X Wang, et al. 2006 Structural identification of methyl protodioscin metabolites in rats' urine and their antiproliferative activities against human tumor cell lines Steroids 71 828 833 16797625
42. P Hebestreit MF Melzig 2003 Cytotoxic activity of the seeds from Agrostemma githago var. githago Planta Med 69 921 925 14648395
43. P Hebestreit A Weng C Bachran, et al. 2006 Enhancement of cytotoxicity of lectins by saponinum album Toxicon 47 330 335 16387336
44. I Heisler M Sutherland C Bachran, et al. 2005 Combined application of saponin and chimeric toxins drastically enhances the targeted cytotoxicity on tumor cells J Cont Release 106 123 137
45. M Henry 2005 Saponins and phylogeny: example of the "gypsogenin group" saponins Phytochem Rev 4 89 94
46. JC Hernández F Leon J Quintana, et al. 2004 Icogenin, a new cytotoxic steroidal saponin isolated from Dracaena draco Bioorg Med Chem Lett 12 16 4423 4429
47. JC Hernández F Leon I Brouard, et al. 2008 Synthesis of novel spirostanic saponins and their cytotoxic activity Bioorg Med Chem 16 4 2063 2076 18023191
48. P Houghton R Fang I Techatanawat, et al. 2007 The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity Methods 42 377 387 17560325
49. Y-L Hsu P-L Kuo T-C Weng, et al. 2004 The antiproliferative activity of saponin-enriched fraction from Bupleurum Kaoi is through Fas-dependent apoptotic pathway in human non-small cell lung cancer A549 Cells Biol Pharm Bull 27 1112 1115 15256750
50. K Hu X Yao 2002 The cytotoxicity of protoneodioscin (NSC-698789), a furostanol saponin from the rhizomes of Dioscorea colletti var. hypoglauca, against human cancer cells in vitro Phytomedicine 9 560 562 12403167
51. K Hu X Yao 2003 The cytotoxicity of methyl protodioscin against human cancer cell lines in vitro Cancer Invest 21 3 389 393 12901285
52. K Hu X Yao 2003 The cytotoxicity of methyl protoneogracillin (NSC-698793) and gracillin (NSC-698787), two steroidal saponins from the rhizomes of Dioscorea colletti var.hypoglauca, against human cancer cells in vitro Phytother Res 17 620 626 12820229
53. C-C Hu J-T Lin S-C Liu, et al. 2007 A spirostanol glycoside from wild yam (Dioscorea villosa) extract and its cytostatic activity on three cancer cells J Food Drug Anal 15 3 310 315
54. H-C Huang M-D Wu W-J Tsai, et al. 2008 Triterpenoid saponins from the fruits and galls of Sapindus mukorossi Phytochemistry 69 1609 1616 18329676
55. H-C Huang C-C Liaw L-J Zhang, et al. 2008 Triterpenoidal saponins from Hydrocotyle sibthorpioides Phytochemistry 69 1597 1603 18329675
56. X-F Huang Y-Y Lin L-Y Kong 2008 Steroids from the roots of Asparagus officinalis and their cytotoxic activity J Integr Plant Biol 50 6 717 722 18713412
57. M Inoue K Ohtani R Kasai, et al. 2009 Cytotoxic 16-β-[(d- xylopyranosyl)oxy] oxohexadecanyl triterpene glycosides from a Malagasy plant, Physena sessiliflora Phytochemistry 70 1195 1202 19604526
58. J-O Jin V-V Shastina S-W Shin, et al. 2009 Differential effects of triterpene glycosides, frondoside A and cucumarioside A2-2 isolated from sea cucumbers on caspase activation and apoptosis of human leukemia cells FEBS Letters 583 697 702 19162021
59. H-J Jung C-O Lee K-T Lee, et al. 2004 Structure-activity relationship of oleanane disaccharides isolated from Akebia quinata versus cytotoxicity against cancer cells and NO inhibition Biol Pharm Bull 27 744 747 15133259
60. M Kalinowska J Zimowski C Pa̧czkowski, et al. 2005 The formation of sugar chains in triterpenoid saponins and glycoalkaloids Phytochem Rev 4 237 257
61. SM Kerwin 2004 Soy saponins and the anticancer effects of soybeans and soy-based foods Curr Med Chem Anticancer Agents 4 263 272 15134504
62. VG Khanna K Kannabiran 2009 Anticancer-cytotoxic activity of saponins isolated from the leaves of Gymnema sylvestre and Eclipta prostrata on HeLa cells Int J Green Pharmacy 3 227 229
63. PV Kiem VK Thu PH Yen, et al. 2009 New triterpenoid saponins from Glochidion eriocarpum and their cytotoxic activity Chem Pharm Bull 57 102 105 19122328
64. J Kim 2008 Protective effects of Asian dietary items on cancers-soy and ginseng Asian Pac J Cancer Prev 9 543 548 19256735
65. Y Kim S-C Bang J-H Lee, et al. 2004 Pulsatilla Saponin D: the antitumor principle from Pulsatilla koreana Arch Pharm Res 27 915 918 15473660
66. G-S Kim H-T Kim J-D Seong, et al. 2005 Cytotoxic steroidal saponins from the rhizomes of Asparagus oligoclonos J Nat Prod 68 5 766 768 15921426
67. 1 in human hepatocellular carcinoma cells through inhibition of telomerase activity and induction of apoptosis Biol Pharm Bull 31 826 830 18451501
68. M-O Kim D-O Moon YH Choi, et al. 2008 Platycodin D induces apoptosis and decreases activity in human leukemia cells Cancer Lett 261 98 107 18093727
69. T Konoshima 1996 Anti-tumor-promoting activities of triterpenoid glycosides; cancer chemoprevention by saponins Adv Exp Med Biol 404 87 100 8957287
70. VV Lemeshko V Haridas JC Quijano Perez, et al. 2006 Avicins, natural anticancer saponins, permeabilize mitochondrial membranes Arch Biochem Biophys 454 114 122 16962987
71. K Li Y Tang JP Fawcett, et al. 2005 Characterization of the pharmacokinetics of dioscin in rat Steroids 70 525 530 15894036
72. M Li S-Y Wei B Xu, et al. 2008 Pro-apoptotic and microtubule-dissasembly effects of ardisiacrispin (A+B), triterpenoid saponins from Ardisia crenata on human hepatoma Bel-7402 cells J Asian Nat Prod Res 10 729 736
73. W Li X Bi K Wang, et al. 2009 Triterpenoid saponins from Impatiens siculifer Phytochemistry 70 816 821 19409580
74. M-J Liang W-D Zhang C Zhang, et al. 2007 Quantitative determination of the anticancer agent tubeimoside I in rat plasma by liquid chromatography coupled with mass spectrometry J Chromatogr B 845 84 89
75. 2+ homeostasis Cancer Chemother Pharmacol 55 79 90 15372201
76. H Liu G-X Chou T Wu, et al. 2009 Steroidal sapogenins and glycosides from the rhizomes of Dioscorea bulbifera J Nat Prod 72 11 1964 1968 19842682
77. R Liu S Ma S Yu, et al. 2009 Cytotoxic oleanane triterpene saponins from Albizia chinensis J Nat Prod 72 632 639 19256478
78. Y Lu J Luo X Huang, et al. 2009 Four new steroidal glycosides from Solanum torvum and their cytotoxic activities Steroids 74 1 95 101 18950652
79. R Ma G Song W You, et al. 2008 Anti-microtubule activity of tubeimoside I and its colchicines binding site of tubulin Cancer Chemother Pharmacol 62 559 568 18030471
80. L Ma YC Gu JG Luo, et al. 2009 Triterpenoid saponins from Dianthus versicolor J Nat Prod 72 640 644 19290648
81. AA Magid L Voutquenne-Nazabadioko I Renimel, et al. 2006 Triterpenoid saponins from the stem bark of Caryocar villosum Phytochemistry 67 2096 2102
82. VS Malisetty JMR Patlolla J Raju, et al. 2005 Chemoprevention of colon cancer by diosgenin, a steroidal saponin constituent of fenugreek Proc Amer Assoc Cancer Res 46 2473
83. S Man W Gao Y Zhang, et al. 2009 Antitumor and antimetastatic activities of Rhizoma Paridis saponins Steroids 74 1051 1056 19699217
84. FR Melek T Miyase NS Ghaly, et al. 2007 Triterpenoid saponins with N-acetyl sugar from the bark of Albizia procera Phytochemistry 68 1261 1266 17408707
85. MF Melzig G Bader R Loose 2001 Investigations of the mechanism of membrane activity of selected triterpenoid saponins Planta Med 67 43 48 11270721
86. MF Melzig P Hebestreit G Gaidi, et al. 2005 Structure-activity relationship of saponins to enhance toxic effects of agrostin Planta Med 71 1088 1090 16320219
87. Y Mimaki A Yokosuka M Kuroda, et al. 2001 Cytotoxic activities and structure-cytotoxic relationships of steroidal saponins Biol Pharm Bull 24 11 1286 1289 11725965
88. L Mskhiladze J Legault S Lavoie, et al. 2008 Cytotoxic steroidal saponins from the flowers of Allium leucanthum Molecules 13 2925 2934 19037184
89. OP Noté AC Mitaine-Offer T Miyamoto, et al. 2009 Cytotoxic acacic acid glycosides from the roots of Albizia coriaria J Nat Prod 72 1725 1730 19778067
90. T Ohtsuki T Koyano T Kowithayakorn, et al. 2004 New chlorogenin hexasaccharide isolated from Agave fourcroydes with cytotoxic and cell cycle inhibitory activities Bioorg Med Chem 12 3841 3845 15210151
91. W Oleszek Z Bialy 2006 Chromatographic determination of plant saponins-an update (2002-2005) J Chromatogr A 1112 78 91 16451803
92. AE Osbourn 2003 Saponins in cereals Phytochemistry 62 1 4 12475612
93. A Perrone A Plaza E Bloise, et al. 2005 Cytotoxic furostanol saponins and a megastigmane glucoside from Tribulus parvispinus J Nat Prod 68 1549 1553 16252924
94. GR Pettit Q Zhang V Pinilla, et al. 2005 Antineoplastic agents. 534. Isolation and structure of Sansevistatins 1 and 2 from the African Sansevieria ehrenbergii J Nat Prod 68 729 733 15921418
95. YK Qiu DQ Dou LP Cai, et al. 2009 Dammarane-type saponins from Panax quinquefolium and their inhibition activity on human breast cancer MCF-7 cells Fitoterapia 80 219 222 19535014
96. H-J Quan J Koyanagi K Ohomori, et al. 2002 Preparations of spirostanols and their pharmacological activities Eur J Med Chem 37 659 669 12161063
97. J Raju R Mehta 2009 Chemopreventive and therapeutic effects of diosgenin, a food saponin Nutr Cancer 61 1 27 35 19116873
98. AV Rao DM Gurfinkel 2000 The bioactivity of saponins: triterpenoid and steroid glycosides Drug Metab Drug Interact 17 211 235
99. AV Rao MK Sung 1995 Saponins as anticarcinogens J Nutr 125 717S 724S 7884557
100. H Ren JP Chen BY Tan, et al. 2008 The disposition and pharmacokinetics of Dioscorea nipponica Makino extract in rats Afr J Biotechnol 7 22 4015 4018
101. Sahu NP, Banerjee S, Mondal NB, Mandal D (2008) Steroidal saponins. In: Fortschritte der Chemie Organischer Naturstoffe/progress in the chemistry of organic natural products, fortschritte der chemie organischer naturstoffe/progress in the chemistry of organic natural products, vol 89. Springer, Vienna, pp 45-141
102. A Sánchez-Medina PC Stevenson S Habtemariam, et al. 2009 Triterpenoid saponins from a cytotoxic root extract of Sideroxylon foetidissimum subsp gaumeri. Phytochemistry 70 765 772
103. M Sautour A-C Mitaine-Offer 2007 The Dioscorea genus: a review of bioactive steroid saponins J Nat Med 61 91 101
104. S Shibata 2001 Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds J Korean Med Sci 16 Suppl S28 S37 11748374
105. F-M Siu D-L Ma Y-W Cheung, et al. 2008 Proteomic and transcriptomic study on the action of a cytotoxic saponin (Polyphyllin D): induction of endoplasmic reticulum stress and mitochondria-mediated apoptotic pathways Proteomics 8 3105 3117 18615425
106. C Sivaramakrishna CV Rao G Trimurtulu, et al. 2005 Triterpenoid glycosides from Bacopa monnieri Phytochemistry 66 2719 2728 16293276
107. D Sobolewska Z Janeczko W Kisiel, et al. 2006 Steroidal glycosides from the underground parts of Allium ursinum L. and their cytostatic and antimicrobial activity Acta Pol Pharm Drug Res 63 2 219 223
108. S Soltysik JY Wu J Recchia, et al. 1995 Structure/function studies of QS-21 adjuvant: assessment of triterpene aldehyde and glucuronic acid roles in adjuvant function Vaccine 13 1403 1410 8578817
109. SG Sparg ME Light J van Staden 2004 Biological activities and distribution of plant saponins J Ethnopharmacol 94 219 243 15325725
110. S Srinivasan S Koduru R Kumar, et al. 2009 Diosgenin targets Akt-mediated prosurvival signaling in human breast cancer cells Int J Cancer 125 961 967 19384950
111. Y Sun T-T Cai X-B Zhou, et al. 2009 Saikosaponin a inhibits the proliferation and activation of T cells through cell cycle arrest and induction of apoptosis Int Immunopharmacol 9 978 983 19375524
112. HX Sun Y Xie YP Ye 2009 Advances in saponin-based adjuvants Vaccine 27 1787 1796 19208455
113. N Tabatadze R Elias R Faure, et al. 2007 Cytotoxic triterpenoid saponins from the roots of Cephalaria gigantea Chem Pharm Bull 55 102 105 17202710
114. LA Tapondjou AC Mitaine-Offer T Miyamoto, et al. 2006 Triterpene saponins from Schefflera abyssinica Bioch System Ecol 34 887 889
115. D Thibeault C Gauthier J Legault, et al. 2007 Synthesis and structure-activity relationship study of cytotoxic germanicane- and lupane-type 3β-O-monodesmosidic saponins starting from betulin Bioorg Med Chem 15 6144 6157 17614290
116. F Tian X Zhang Y Tong, et al. 2005 PE, a new sulfated saponin from sea cucumber, exhibits anti-angiogenic and anti-tumor activities in vitro and in vivo Cancer Biol Therapy 4 874 882
117. J Tian L Xu Z Zou, et al. 2006 New antitumor triterpene saponin from Lysimachia capillipes Chem Nat Compd 42 328 331
118. Y Tian HF Tang F Qiu, et al. 2009 Triterpenoid saponins from Ardisia pusilla and their cytotoxic activity Planta Med 75 70 75 19039733
119. P Trouillas C Corbiere B Liagre, et al. 2005 Structure-function relationship for saponin effects on cell cycle arrest and apoptosis in the human 1547 osteosarcoma cells: a molecular modeling approach of natural molecules structurally close to diosgenin Bioorg Med Chem 13 1141 1149 15670922
120. R Tundis M Bonesi B Deguin, et al. 2009 Cytotoxic activity and inhibitory effect on nitric oxide production of triterpene saponins from the roots of Physospermum verticillatum (Waldst & Kit) (Apiaceae) Bioorg Med Chem 17 4542 4547 19467877
121. JP Vincken L Heng A de Groot, et al. 2007 Saponins, classification and occurence in the plant kingdom Phytochemistry 68 275 297 17141815
122. Z Wang J Zhou Y Ju, et al. 2001 Effects of two saponins from the Polygonatum zanlanscianense Pamp on the human leukemia (HL-60) cells Biol Pharm Bull 24 2 159 162 11217084
123. G Wang H Chen M Huang, et al. 2006 Methyl protodioscin induces G2/M cell cycle arrest and apoptosis in HepG2 live cancer cells Cancer Lett 241 1 102 109 16458429
124. Y Wang Y Zhang Z Zhu, et al. 2007 Exploration of the correlation between the structure, hemolytic activity, and cytotoxicity of steroid saponins Bioorg Med Chem 15 2528 2532 17306549
125. X-H Wang B Xu J-T Liu, et al. 2008 Effect of β-escin sodium on endothelial cells proliferation, migration and apoptosis Vasc Pharmacol 49 158 165
126. J Wang X-Z Zhao Q Qi, et al. 2009 Macranthoside B, a hederagenin saponin extracted from Lonicera macranthoides and its anti-tumor activities in vitro and in vivo Food Chem Toxicol 47 1716 1721 19406196
127. A Weng C Görick MF Melzig 2009 Enhancement of toxicity of saporin-based toxins by Gypsophilla saponins-kinetic of the saponin Exp Biol Med 234 961 966
128. B-B Xie H-Y Liu W Ni, et al. 2009 Ypsilandrosides C-G, five new spirostanol saponins from Ypsilandra thibetica Steroids 74 950 955 19595698
129. J Xiong J Guo L Huang, et al. 2008 Self-micelle formation and the incorporation of lipid in the formulation affect the intestinal absorption of Panax notoginseng Int J Pharm 360 191 196 18502060
130. Z-X Xu J Liang V Haridas, et al. 2007 A plant triterpenoid, avicin D, induces autophagy by activation of AMP-activated protein kinase Cell Death Differ 14 1948 1957 17690712
131. FQ Xu HM Zhong HY Liu, et al. 2007 Steroidal saponins from Lysimachia Paridiformis J Asian Nat Prod Res 9 493 497 17885834
132. Y Xu JF Chiu Q-Y He, et al. 2009 Tubeimoside-1 exerts cytotoxicity in HeLa cells through mitochondrial dysfunction and endoplasmic reticulum stress pathways J Proteome Res 8 1585 1593 19215086
133. LL Yan YJ Zhang WY Gao, et al. 2009 In vitro and in vivo anticancer activity of steroid saponins of Paris polyphylla var. yunanensis Exp Oncol 31 1 27 32 19300413
134. Q-X Yang C-R Yang 2006 Cytotoxic steroidal saponins from Polygonatum punctatum Chem Biodiver 3 1349 1355
135. C-R Yang Y Zhang MR Jacob, et al. 2006 Antifungal activity of C-27 steroidal saponins Antimicrob Agents Chemother 50 5 1710 1714 16641439
136. A Yokosuka Y Mimaki 2009 Steroidal saponins from the whole plants of Agave utahensis and their cytotoxic activity Phytochemistry 70 807 815 19394982
137. A Yokosuka M Jitsuno S Yui, et al. 2009 Steroidal glycosides from Agave utahensis and their cytotoxic activity J Nat Prod 72 1399 1404 19645463
138. B Yu J Sun 2009 Current synthesis of triterpene saponins Chem Asian J 4 642 654 19294723
139. T-X Yu R-D Ma L-J Yu 2001 Structure-activity relationship of tubeimosides In anti-inflammatory, antitumor, and antitumor-promoting effects Acta Pharmacol Sin 22 463 468 11743898
140. B Yu Y Zhang P Tang 2007 Carbohydrate chemistry in the total synthesis of saponins Eur J Org Chem 31 5145 5161
141. L Yu JZ Yang XG Chen, et al. 2009 Cytotoxic triterpenoid glycosides from the roots of Gordonia chrysandra J Nat Prod 72 866 870 20560647
142. H Yun C Lijan Z Wenhong, et al. 2007 Separation and identification of steroidal compounds with cytotoxic activity against human gastric cancer cell lines in vitro from the rhizomes of Paris polyphylla var. chinensis Chem Nat Compd 43 6 672 677
143. Z Zhang S Li 2007 Cytotoxic triterpenoid saponins from the fruits of Aesculus pavia L Phytochemistry 68 2075 2086 17599369
144. SY Zhang HF Tang YH Yi 2007 Cytotoxic triterpene glycosides from the sea cucumber Pseudocolochirus violaceus Fitoterapia 78 283 287 17493770
145. C Zhang B Li AS Gaikwad, et al. 2008 Avicin D selectively induces apoptosis and downregulates p-STAT-3, bcl-2, and survivin in cutaneous T-cell lymphoma cells J Invest Dermatol 128 2728 2735 18496567
146. Y Zhao L-P Kang Y-X Liu, et al. 2009 Steroidal saponins from the rhizome of Paris polyphylla and their cytotoxic activities Planta Med 75 356 363 19085682
147. X Zhou X He G Wang, et al. 2006 Steroidal saponins from Solanum nigrum J Nat Prod 69 8 1158 1163 16933867
148. L-B Zhou T-H Chen KF Bastow, et al. 2007 Filiasparosides A-D, cytotoxic steroidal saponins from the roots of Asparagus filicinus J Nat Prod 70 1263 1267 17629328
149. K Zou J Wang M Du, et al. 2006 A pair of diastereoisomeric steroidal saponins from cytotoxic extracts of Tupistra chinensis rhizomes Chem Pharm Bull 54 10 1440 1442 17015986
150. K Zou YY Zhao RY Zhang 2006 A cytotoxic saponin from Albizia julibrissin Chem Pharm Bull 54 1211 1212 16880673