• NESTI FRONIKA SIANIPAR Department of Food Technology, Faculty of Engineering, Bina Nusantara University, Jakarta 11480, Indonesia.
  • KHOIRUNNISA ASSIDQI Research Interest Group Food Biotechnology, Bina Nusantara University, Jakarta 11480, Indonesia.
  • RAGAPADMI PURNAMANINGSIH Indonesian Center for Agricultural Biotechnology and Genetic Resources Research and Development (BB-Biogen), 16111 Bogor, Indonesia.
  • TATI HERLINA Department of Chemistry, Mathematics and Science Faculty, Padjajaran University, Jatinangor 45363, Sumedang, Indonesia.


Objective: The objective of this study was to determine the new bioactive compounds through gas chromatography–mass spectrometry analysis and the cytotoxic activity of two rodent tuber mutant plants against breast cancer cells (MCF-7).

Methods: The bioactive compounds in rodent tuber mutant plants were successfully increased by somaclonal variation using gamma rays irradiation technique. Further, the cytotoxicity activity of rodent tuber mutant plants was tested on breast cancer cell line (MCF-7) performed by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assay method.

Results: This results study confirmed that the presence of phytochemical composition in the tuber of rodent tuber mutant plants KB 6–1–3–4 and KB 6–9–5 was found six bioactive compounds from fatty acid groups which have the potential as an anticancer compound, such as octadecanoic acid, hexadecanoic acid, hexadecanoic acid methyl ester, 9-octadecanoic acid, linolelaidic acid methyl ester, and butanoic acid. The results showed that extracts from rodent tuber mutant plants had a cytotoxicity effect on MCF-7 cancer cells with half maximal inhibitory concentration (IC50) values that were lower than the control (mother plant). In vitro tests of KB 6–1–3–4 and KB 6–9–5 against MCF-7 cancer cell lines have IC50 values of 12.482 μg/mL and 7.043 μg/mL, respectively, while it had a lower cytotoxicity effect with the IC50 value of control plant was 19.113 μg/mL. The mutant plants of KB 6-9-5 have 3 times more effective than control.

Conclusion: The results of this study clearly indicated that rodent tuber mutant plants have shown promising as an anticancer drug on breast cancer.

Keywords: Typhonium flagelliforme Lodd., Anticancer, MCF-7 cell, Gas chromatography–mass spectrometry analysis, Fatty acids.


1. Essai. Medicinal Herbs Index in Indonesia. Jakarta: PT Essai Indonesia; 1986.
2. Lai CS, Mas RH, Nair NK, Majid MI, Mansor SM, Navaratnam V, et al. Typhonium flagelliforme inhibits cancer cell growth in vitro and induces apoptosis: An evaluation by the bioactivity guided approach. J Ethnopharmacol 2008;118:14-20.
3. Mankaran S, Dinesh K, Deepak S, Gurmeet S. Typhonium flagelliforme: A multipurpose plant. Int Res J Pharm 2013;4:45-8.
4. Mohan S, Bustamam A, Ibrahim S, Al-Zubairi AS, Aspollah M. Anticancerous effect of Typhonium flagelliforme on human T4- Lymphoblastoid cell line CEM-ss. J Toxicol Pharmacol 2008;3:449-56.
5. Mohan S, Abdul AB, Abdelwahab SI, Al-Zubairi AS, Aspollah Sukari M, Abdullah R, et al. Typhonium flagelliforme inhibits the proliferation of murine leukemia WEHI-3 cells in vitro and induces apoptosis in vivo. Leuk Res 2010;34:1483-92.
6. Mohan S, Bustamam A, Ibrahim S, Al-Zubairi AS, Aspollah M, Abdullah R, et al. In vitro ultramorphological assessment of apoptosis on CEMss induced by linoleic acid-rich fraction from Typhonium flagelliforme tuber. Evid Based Complement Alternat Med 2011;2011:421894.
7. Sianipar NF, Laurent D, Purnamaningsih R, Darwati I. The Effect of Gamma Irradiation and Somaclonal Variation on Morphology Variation of Mutant Rodent Tuber (Typhonium flagelliforme Lodd) Lines. Indonesia: Proceeding International Conference on Biological Science ICBS UGM; 2013.
8. Sianipar NF, Purnamaningsih R, Gumanti DL, Rosaria, Vidianty M. Analysis of gamma irradiated-third generation mutants of rodent tuber (Typhonium flagelliforme Lodd.) based on morphology, RAPD, and GC-MS markers. Pertanika J Trop Agric Sci 2017;40:185-202.
9. Sianipar NF, Purnamaningsih R, Gumanti DV, Rosaria, Vidianty M. Analysis of gamma irradiated fourth generation mutant of rodent tuber (Typhonium flagelliforme Lodd.) based on morphology and RAPD markers. J Teknol 2016;78:41-9.
10. Sianipar NF, Purnamaningsih R, Chelen C. Effect of gamma irradiation on protein profile of rodent tuber (Typhonium flagelliforme Lodd.) in vitro mutant based on 1D and 2D page analyses. J Teknol 2016;78:35-40.
11. Sianipar NF, Purnamaningsih R. Enhancement of the contents of anticancer bioactive compounds in mutant clones of rodent tuber (Typhonium flagelliforme Lodd.) based on GC-MS analysis. Pertanika J Trop Agric Sci 2018;41:305-20.
12. Marimuthu S, Padmaja B, Nair S. Phytochemical screening studies on Melia orientalis by GC-MS analysis. Pharmacognosy Res 2013;5:216-8.
13. Nishaa S, Vishnupriya M, Sasikumar JM, Gopalakrishnan VK. Phytochemical screening and GC-MS analysis of ethanolic extract of rhizomes of Maranta arudinacea L. Res J Pharm Biol Chem Sci 2013;4:52-9.
14. Nurrochmad A, Lukitaningsih E, Meiyanto E. Anticancer activity of rodent tuber (Typhonium flagelliforme (Lodd.) blume on human breast cancer T47D cells. Int J Phytomed 2011;2:138-46.
15. Munshi A, Hobbs M, Meyn RE. Clonogenic cell survival assay. Methods Mol Med 2005;110:21-8.
16. Rajendran V, Jain MV. In vitro tumorigenic assay: Colony forming assay for cancer stem cells. Methods Mol Biol 2018;1692:89-95.
17. Durgawale TP, Khanwelkar CC, Durgawale PP. Phytochemical analysis of Portulaca oleracea and Portulaca quadrifida extracts using gas chromatography-mass spectrometry. Asian J Pharm Clin Res 2018;11:204-7.
18. Praptiwi P, Fathoni A. Phytochemical, gas chromatography-mass spectrometry profiling and free radical scavenging activity of Exocarpos longifolius (Santalaceae) extracts. Asian J Pharm Clin Res 2018;11:452-6.
19. Lakshmi PT, Rajalakshmi P. Identification of phyto-components and its biological activities of Aloe vera through the gas chromatography-mass spectrometry. Int Res J Pharm 2011;2:247-9.
20. Yoo YC, Shin BH, Hong JH, Lee J, Chee HY, Song KS, et al. Isolation of fatty acids with anticancer activity from Protaetia brevitarsis Larva. Arch Pharm Res 2007;30:361-5.
21. Harada H, Yamashita U, Kurihara H, Fukushi E, Kawabata J, Kamei Y, et al. Antitumor activity of palmitic acid found as a selective cytotoxic substance in a marine red alga. Anticancer Res 2002;22:2587-90.
22. Khan AA, Alanazi AM, Jabeen M, Chauhan A, Abdelhameed AS. Design, synthesis and in vitro anticancer evaluation of a stearic acid-based ester conjugate. Anticancer Res 2013;33:2517-24.
23. Brueckner B, Rius M, Markelova MR, Fichtner I, Hals PA, Sandvold ML, et al. Delivery of 5-azacytidine to human cancer cells by elaidic acid esterification increases therapeutic drug efficacy. Mol Cancer Ther 2010;9:1256-64.
24. Chujo H, Yamasaki M, Nou S, Koyanagi N, Tachibana H, Yamada K, et al. Effect of conjugated linoleic acid isomers on growth factor-induced proliferation of human breast cancer cells. Cancer Lett 2003;202:81-7.
25. Inagaki A, Sakata T. Dose-dependent stimulatory and inhibitory effects of luminal and serosal n-butyric acid on epithelial cell proliferation of pig distal colonic mucosa. J Nutr Sci Vitaminol (Tokyo) 2005;51:156-60.
26. Kim SW, Hooker JM, Otto N, Win K, Muench L, Shea C, et al. Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET. Nucl Med Biol 2013;40:912-8.
27. Komata T, Kanzawa T, Nashimoto T, Aoki H, Endo S, Kon T, et al. Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8-but not caspase-9-dependent apoptosis in human malignant glioma cells. Int J Oncol 2005;26:1345-52.
28. Abdel-Hameed ES, Salih A, Bazaid SA, Shohayeb MM, El-Sayed MM, El-Wakil EA. Phytochemical studies and evaluation of antioxidant, anticancer and antimicrobial properties of Conocarpus erectus L. growing in Taif, Saudi Arabia. Eur J Med Plants 2012;2:93-12.
29. Boik J. Natural Compounds in Cancer Therapy. Minnesota, USA: Oregon Medical Press; 2001.
30. Rahmoune B, Zerraouk IZ, Morsli A, Khelifi-Slaoui M, Khelifi L, Amarante LD. Phenylpropanoids and fatty acids levels in roots and leaves of Datura stramonium and Datura innoxia. Int J Pharm Pharm Sci 2017;9:150-4.
31. Evans LM, Cowey SL, Siegal GP, Hardy RW. Stearate preferentially induces apoptosis in human breast cancer cells. Nutr Cancer 2009;61:746-53.
32. Hardy RW, Wickramasinghe NS, Ke SC, Wells A. Fatty acids and breast cancer cell proliferation. Adv Exp Med Biol 1997;422:57-69.
33. Wickramasinghe NS, Jo H, McDonald JM, Hardy RW. Stearate inhibition of breast cancer cell proliferation. A mechanism involving epidermal growth factor receptor and G-proteins. Am J Pathol 1996;148:987-95.
34. Evans LM, Toline EC, Desmond R, Siegal GP, Hashim AI, Hardy RW, et al. Dietary stearate reduces human breast cancer metastasis burden in athymic nude mice. Clin Exp Metastasis 2009;26:415-24.
35. Iyer VV, Griesgraber GW, Radmer MR, McIntee EJ, Wagner CR. Synthesis, in vitro anti-breast cancer activity, and intracellular decomposition of amino acid methyl ester and alkyl amide phosphoramidate monoesters of 3’-azido-3’-deoxythymidine (AZT).J Med Chem 2000;43:2266-74.
36. Li C, Zhao X, Toline EC, Siegal GP, Evans LM, Ibrahim-Hashim A, et al. Prevention of carcinogenesis and inhibition of breast cancer tumor burden by dietary stearate. Carcinogenesis 2011;32:1251-8.
37. Saadatian-Elahi M, Norat T, Goudable J, Riboli E. Biomarkers of dietary fatty acid intake and the risk of breast cancer: A meta-analysis. Int J Cancer 2004;111:584-91.
38. Paul S, Kundu R. Induction of apoptosis by fatty acid rich fraction of Solanum nigrum on cervical cancer cell lines. Int J Pharm Pharm Sci 2017;9:199-206.
39. Yu FR, Lian XZ, Guo HY, McGuire PM, Li RD, Wang R, et al. Isolation and characterization of methyl esters and derivatives from Euphorbia kansui (Euphorbiaceae) and their inhibitory effects on the human SGC- 7901 cells. J Pharm Pharm Sci 2005;8:528-35.
40. Kim YS, Li XF, Kang KH, Ryu B, Kim SK. Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma hepG2 cells. BMB Rep 2014;47:433-8.
41. Mericli F, Becer E, Kabaday? H, Hanoglu A, Yigit Hanoglu D, Ozkum Yavuz D, et al. Fatty acid composition and anticancer activity in colon carcinoma cell lines of Prunus dulcis seed oil. Pharm Biol 2017;55:1239-48.
42. Sabithira G, Udayakumar R. GC–MS analysis of methanolic extracts of leaf and stem of Marsilea minuta (Linn.). J Altern Complement Med 2017;3:1-13.
43. Purwaningsih E, Widayanti E, Suciati Y. Cytotoxicity assay of Typhonium flagelliforme Lodd against breast and cervical cancer cells. Univ Med 2014;33:75-82.
44. Purwaningsih E, Suciati Y, Widayanti E. Typhonium flagelliforme decreases telomerase expression in HeLa cervical cancer cells. Univ Med 2016;35:3-9.
45. Purwaningsih E, Suciati Y, Widayanti E. Anticancer effect of a Typhonium flagelliforme L. in raji cells through telomerase expression. Indones J Cancer Chemoprevent 2017;8:15-20.
46. Jin G, You Y, Ahn B. Esters of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10- anthraquinones with melphalan as multifunctional anticancer agents. Bioorg Med Chem Lett 2001;11:1473-6.
47. Hardy S, El-Assaad W, Przybytkowski E, Joly E, Prentki M, Langelier Y, et al. Saturated fatty acid-induced apoptosis in MDA-MB-231 breast cancer cells. A role for cardiolipin. J Biol Chem 2003;278:31861-70.
11 Views | 15 Downloads
How to Cite
Original Article(s)