Planta Med 2015; 81(18): 1705-1711
DOI: 10.1055/s-0035-1557751
Biological and Pharmacological Activitiy
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Evaluation of Cytotoxic and Antitumour Properties of Apodytes dimidiata and Characterisation of the Bioactive Component

Menon Kunnathully Divya
Department of Biochemistry, Amala Cancer Research Centre (Affiliated to University of Calicut), Amala Nagar, Thrissur, Kerala, India
,
Sasidharan Salini
Department of Biochemistry, Amala Cancer Research Centre (Affiliated to University of Calicut), Amala Nagar, Thrissur, Kerala, India
,
Thomas Chubicka
Department of Biochemistry, Amala Cancer Research Centre (Affiliated to University of Calicut), Amala Nagar, Thrissur, Kerala, India
,
Achuthan Chathrattil Raghavamenon
Department of Biochemistry, Amala Cancer Research Centre (Affiliated to University of Calicut), Amala Nagar, Thrissur, Kerala, India
,
Thekkekara Devassy Babu
Department of Biochemistry, Amala Cancer Research Centre (Affiliated to University of Calicut), Amala Nagar, Thrissur, Kerala, India
› Author Affiliations
Further Information

Publication History

received 29 July 2014
revised 10 June 2015

accepted 12 June 2015

Publication Date:
28 July 2015 (online)

Abstract

Apodytes dimidiata, belonging to the family Icacinaceae, is used for treating inflammation and various gastrointestinal ailments in Zulu traditional medicine. In the present study, significant cytotoxicity was exhibited by the methanolic extract of the A. dimidiata leaf against various cancer cell lines. The extract was purified partially through silica gel column by successive elution using various solvents of increasing polarity. Among these, the active methanolic fraction was found to be the most cytotoxic with IC50 values ranging from 0.92 to 3.95 µg/mL for Ehrlichʼs ascites carcinoma (a carcinoma cell line), Jurkat (human T lymphocyte cell line), and SK-BR-3 (mammary tumour cell line). The treated cells showed morphological alterations characteristic of apoptosis. Upon oral administration of active methanolic fraction at a dose of 250 mg/kg body weight, the solid tumour volume in mice was significantly reduced to 55.14 % and the life span of the ascites tumour-bearing mice increased to 44.65 % compared to untreated control. The active fraction with Rf value 0.56 was purified from the methanolic fraction by preparative thin-layer chromatography and was subjected to high-performance thin-layer chromatography, high-performance liquid chromatography, liquid chromatography-mass spectrometry, and nuclear magnetic resonance analysis. The iridoid glycoside genipin was identified as the active component.

Supporting Information

 
  • References

  • 1 Hamedeyazdan S, Fathiazad F, Sharifi S, Nazemiyeh H. Antiproliferative activity of Marrubium persicum extract in the MCF7 human breast cancer cell line. Asian Pac J Cancer Prev 2012; 13: 5843-5848
  • 2 Suttana W, Mankhetkorn S, Poompimon W, Palagani A, Zhokhov S, Gerlo S. Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols. Mol Cancer 2010; 9: 99
  • 3 Gestner J. A preliminary checklist of Zulu names of plants with short notes. Bantu Studies 1938; 12: 321-342
  • 4 Bryant AT. Zulu medicine and medicine-men. Cape Town: Struik; 1966
  • 5 Hutchings A, Scott AH, Lewis G, Cunningham AB. Zulu medicinal plants: an inventory. Pietermaritzburg: University of Natal Press; 1996
  • 6 Watt JM, Breyer-Brandwijk MG. The medicinal and poisonous plants of southern and eastern Africa. 2nd edition.. Edinburgh: E & S Livingstone; 1962
  • 7 Ramesha BT, Suma HK, Senthilkumar U, Priti V, Ravikanth G, Vasudeva R, Santhosh Kumar TR, Ganeshaiah KN, Shaanker RU. New plant sources of the anti-cancer alkaloid, camptothecine from the Icacinaceae taxa, India. Phytomedicine 2013; 20: 521-527
  • 8 Shweta S, Zuehlke S, Ramesha BT, Priti V, Mohana KP, Ravikanth G, Spiteller M, Vasudeva R, Uma Shaanker R. Endophytic fungal strains of Fusarium solani, from Apodytes dimidiata E. Mey.ex Arn (Icacinaceae) produce camptothecin, 10-hydroxycamptothecin and 9-methoxycamptothecin. Phytochemistry 2010; 71: 117-122
  • 9 Drewes SE, Kayonga L, Clark TE, Brackenbury TD, Appleton CC. Iridoid molluscicidal fractions from Apodytes dimidiata . J Nat Prod 1996; 59: 1169-1170
  • 10 Harinantenaina L, Mananjarasoa E, Yamasaki K. An acetylated eudesmane glucoside from Apodytes dimidiata growing in Madagascar. Z Naturforsch 2006; 61: 113-115
  • 11 Koo HJ, Song YS, Kim HJ, Lee YH, Hong SM, Kim SJ, Kim BC, Jin C, Lim CJ, Park EH. Anti inflammatory effects of genipin, an active principle of Gardenia. Eur J Pharmacol 2004; 495: 201-208
  • 12 Cao JP, Wang YL, Jia YJ. Simultaneous determination of geniposide and genipin in Gardenia jasminoides Ellis by high performance liquid chromatography. J Dalian Med Univ 2001; 23: 61-62
  • 13 Foubert K, Cuyckens F, Matheeussen A, Vlietinck A, Apers S, Maes L, Pieters L. Anti-protozoal and anti-angiogenic saponins from Apodytes dimidiata . Phytochemistry 2011; 72: 1414-1423
  • 14 Brackenbury TD, Appleton CC, Thurman G. Mammal toxicity assessment of the plant molluscicide, Apodytes dimidiata (Icacinaceae), in South Africa. Acta Trop 1997; 65: 155-162
  • 15 Abdel-Hameed ES, Salih A, Bazaid SA, Shohayeb MM, El-Sayed MM, El-Wakil EA. Phytochemical studies and evaluation of anti-oxidant, anti-cancer and anti-microbial properties of Conocarpus erectus L. growing in Taif, Saudi Arabia. Eur J Med Plants 2012; 2: 93-112
  • 16 Mahavorasirikul W, Viyanant V, Chaijaroenkul W, Itharat A, Na-Bangchang K. Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro . BMC Complement Altern Med 2010; 10: 55
  • 17 Clarkson D, Burchneal JH. Preliminary screening of anti-neoplastic drugs. Prog Clin Cancer 1965; 1: 625-629
  • 18 Hutchings A. A survey and analysis of traditional medicinal plants as used by the Zulu, Xhosa and Sotho. Bothalio 1989; 19: 111-123
  • 19 Fujikama S, Fukui Y, Koga K, Kumada J. Brilliant skyblue pigment formation from Gardenia fruits. J Ferment Technol 1987; 65: 419-424
  • 20 Hou YC, Tsai SY, Lai PY. Metabolism and pharmacokinetics of genipin and geniposide in rats. Food Chem Toxicol 2008; 46: 2764-2769
  • 21 Park JE, Lee JY, Kim HG, Hahn TR, Paik YS. Isolation and characterization of water-soluble intermediates of blue pigments transformed from geniposide of Gardenia jasminoides . J Agric Food Chem 2002; 50: 6511-6514
  • 22 Zhang CY, Parton LE, Ye CP, Krauss S, Shen R, Lin CT, Porco JA, Lowell BB. Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets. Cell Metab 2006; 3: 417-427
  • 23 Hwa JS, Mun L, Kim HJ, Seo HG, Lee JH, Kwak JH, Lee DU, Chang KC. Genipin selectively inhibits TNF-α-activated VCAM-1 but not ICAM-1 expression by upregulation of PPAR-γ in human endothelial cells. Korean J Physiol Pharmacol 2011; 15: 157-162
  • 24 Lelono RA, Achibana S, Itoh K. Isolation of anti-fungal fractions from Gardenia jasminoides . Pak J Biol Sci 2009; 12: 946-956
  • 25 Wang N, Zhu M, Tsao S, Man K, Zhang Z, Feng Y, Salvatore VP. Up-regulation of TIMP-1 by genipin inhibits MMP-2 activities and suppresses the metastatic potential of human hepatocellular carcinoma. PLoS One 2012; 7: e46318
  • 26 Cao H, Feng Q, Xu W, Li X, Kang Z, Ren Y, Du L. Genipin induced apoptosis associated with activation of the c-Jun NH2-terminal kinase and p 53 protein in HeLa cells. Biol Pharm Bull 2010; 33: 1343-1348
  • 27 Zhou H, Zhao J, Zhang X. Inhibition of uncoupling protein 2 by genipin reduces insulin stimulated glucose uptake in 3T3-L1 adipocytes. Arch Biochem Biophys 2009; 486: 88-93
  • 28 Valle A, Oliver J, Roca P. Role of uncoupling proteins in cancer. Cancers (Basel) 2010; 2: 567-591
  • 29 Talwar GP. Handbook of practical immunology. New Delhi: National Book Trust; 1974: 329
  • 30 Mosmann T. Rapid colorometric assays for cellular growth and survival applications to proliferation and cytotoxic assays. J Immunol Methods 1983; 65: 55-63
  • 31 Jefferson MF, Pendleton N, Faragher EB, Dixon GR, Myskow MW, Horan MA. Tumor volume as a predictor of survival after resection of non-small-cell lung cancer (NSCLC). Br J Cancer 1996; 74: 456-459