Abstract
The root extract of Eurycoma longifolia Jack has been shown to be effective against different type of cancers. Present study was carried out to study the effect of three biotic elicitors, yeast extract, pectin, and valine, on the cytotoxicity activity of the bioactive compounds produced in the cell suspension culture of E. longifolia against human colon cancer cell lines. Yeast extract consists of vitamin B complex, chitin, N-acetyl-glucosamin, β-glucan, glycopeptide, and ergosterol, while pectin contains cell wall components. Yeast extract and pectin, along with the branched chain amino acid valine, were evaluated as biotic elicitors to trigger the production of plant defense–related compounds. The different stages of cell growth influenced the production of the bioactive compounds; hence the administration of the elicitors at different stage of cell growth is vital for enhancement of their production. The results showed that all three biotic elicitors were effective in enhancing cytotoxic activity similar to that of root extract from the mature plant against human colon cancer cell line, HCT116, without affecting its cell growth. Crude extract derived from cells elicited with 2.0 g L−1 pectin supplemented on the 17th d showed good inhibition of HCT116 cell proliferation with IC50 of 19.4 μg mL−1. Hence, cell suspension culture of E. longifolia with elicitation is an alternative time-saving tool for production of valuable anti-cancer compounds and the conservation of this valuable plant due to indiscriminate harvesting from its natural habitat.
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Abbade LC, Paiva PDD, Paiva R, Graciano MHP (2010) Growth curve and biochemical analyses of callus of IPE-BRANCO (Tabebuia roseo alba (Ridl.) Sand.). Naturalia 33:45–56
Al-Salahi OSA, Ji D, Majid AMSA, Kit-Lam C, Abdullah WZ, Zaki A, Din SKKJ, Yusoff NM, Majid ASA (2014) Anti-tumor activity of Eurycoma longifolia root extracts against K-562 cell line: in vitro and in vivo study. PLoS One 9:1–13
Al-Salahi OSA, Zaki AH, Chan KL, Shah AM, Al-Hassan F, Abdullah WZ, Yusoff NM (2013) In vitro anti-proliferative and apoptotic activities of Eurycoma longifolia jack (simaroubaceae) on HL-60 cell line. Trop J Pharm Res 12:57–61
Alttaher AGA, Yusof ZNB, Mahmood M, Shaharuddin NA (2020) High-frequency induction of multiple shoots and plant regeneration from cotyledonary node explants of Tongkat Ali (Eurycoma longifolia Jack). Appl Ecol Environ Res 18:6321–6333
Anderson PC, Hibberd KA (1985) Evidence for the interaction of an imidazolinone herbicide with leucine, valine and isoleucine metabolism. Weed Sci 33:479–483
Ashtiani SR, Hasanloo T, Bihamta MR (2010) Enhanced production of silymarin by Ag+ elicitor in cell suspension cultures of Silybum marianum. Pharm Biol 48:708–715
Baque MA, Shiragi MHK, Lee EJ, Paek KY (2012) Elicitor effect of chitosan and pectin on the biosynthesis of anthraquinones, phenolics and flavonoids in adventitious root suspension cultures of Morinda citrifolia (L.). Austral J Crop Sci 6:1349–1355
Cai Z, Kastell A, Mewis I, Knorr D, Smetanska I (2012) Polysaccharide elicitors enhance anthocyanin and phenolic acid accumulation in cell suspension cultures of Vitis vinifera. Plant Cell Tiss Org Cult 108:401–409
Chan LK, Ang SW, Bhatt A (2010) Elicitation effect on cell biomass and production of alkaloids in cell suspension culture of the tropical tree Eurycoma longifolia. UNED Res J 2:239–244
Chee FM, Rathinam X, Danial M, Chan KL, Qui MH, Subramaniam S (2015) Effects of methyl-jasmonate on 9-methoxycanthin-6-one content in Eurycoma longifolia (Tongkat Ali) root culture. Pak J Bot 47:897–904
Cho HY, Son SY, Rhee HS, Yoon SYH, Lee-Parsons CWT, Park JM (2008) Synergistic effects of sequential treatment with methyl jasmonate, salicylic acid and yeast extract on benzophenonthridine alkaloid accumulation and protein expression in Eschscholtzia californica suspension cultures. J Biotechnol 135:117–122
Cosgrove DJ (2016) Plant cell wall extensibility: connecting plant cell growth with cell wall structure, mechanics, and the action of wall-modifying enzymes. J Exp Bot 67:463–476
Cragg GM, Newman DJ (2006) Anticancer drug discovery and development from natural products. In: Colegate SM, Molyneux RJ (eds) Bioactive natural products: direction, isolation and structure determination, 2nd edn. CRC Press/ Taylor and Francis, London, pp 323–370
Dang NH, Lan DTN, Minh NTT, Khanh ND, Trang DT, Van Cuong P, Hiep NT, Nam VD, Trung NQ, Dat NT (2019) Quassinoids and alkaloids from the roots of Eurycoma longifolia. Nat Prod Commun 14:1–4
Diaz JV, Anthon GE, Barrett DM (2007) Nonenzymatic degradation of citrus pectin and pectate during prolonged heating: effects of pH, temperature, and degree of methyl esterification. J Agric Food Chem 55:5131–5136
Effendy MN, Mohamed N, Muhammad N, Naina Mohamad I, Shuid AN (2012) Eurycoma longifolia: medicinal plant in the prevention and treatment of male osteoporosis due to androgen deficiency. Evid Based Complement Alternat Med 2012:1–9
Ezzat SM, Okba MM, Ezzat MI, Aborehab NM, Mohamed SO (2019) Rho-kinase II inhibitory potential of Eurycoma longifolia new isolate for the management of erectile dysfunction. Evid Based Complement Alternat Med 2019:1–8
Fan G, Nie T, Fan JS, Zhan Y (2017) Exogenous feeding of fructose and phenylalanine further improves betulin production in suspended Betula platyphylla cells under nitric oxide treatment. Molecules 22:1–11
Ferrari CC, Sarantópoulos CIGL, Carmello-Guerreiro SM, Hubinger MD (2013) Effect of osmotic dehydration and pectin edible coatings on quality and shelf life of fresh-cut melon. Food Bioprocess Technol 6:80–91
Goreja WG (2004) Tongkat Ali: the tree that cures a hundred diseases, vol 2. Amazing Herb Press, New York
Grodoy-Hernandez G, Vazquez-Flota F (2012) Growth measurements: estimation of cell division and cell expansion. In: Loyota-Vargas VM, Vazquez-Flota F (eds) Plant cell culture protocols. Humana Press, Totowa, pp 51–59
Haas KT, Wightman R, Meyerowitz EM, Peaucelle A (2020) Pectin homogalacturonan nanofilament expansion drives morphogenesis in plant epidermal cells. Science 367:1003–1007
Hajjouli S, Chateauvieux S, Teiten MH, Orlikova B, Schumacher M, Dicato M, Choo CY, Diederich M (2014) Eurycomanone and eurycomanol from Eurycoma longifolia Jack as regulators of signaling pathways involved in proliferation, cell death and inflammation. Molecules 19:14649–14666
Hendra P, Fenty APR, Pangestuti BME, Julianus J (2017) Evaluation of antihyperlipidemic, anti-inflammatory, and analgesic activities of Eurycoma longifolia in Animal Models. Int J Pharm Pharm Sci 9:166–169
Hou WB, Xiao XF, Gou W, Zhang TJ (2011) Advances in studies on chemistry, pharmacological effect and pharmacokinetics of Eurycoma longifolia. Chin Herb Med 3:186–195
Hsuan K (1983) Orders and families of Malayan seed plants, 3rd edn. Singapore University Press, Singapore
Hu X, Neil S, Cai W, Tang Z (2003) Hydrogen peroxide and jasmonic acid mediate oligogalacturonic acid-induced saponin accumulation in suspension-cultured cells of Panax ginseng. Physiol Plant 118:414–421
Hussein S, Ibrahim R, Kiong ALP, Fadzil NM, Daud SK (2005) Micropropagation of Eurycoma longifolia Jack via formation of somatic embryogenesis. Asian J Plant Sci 4:472–485
Jamal JA (2006) Malay traditional medicine: an overview of scientific and technological progress. Tech Monitor, Nov-Dec, 37–49
Jiwajinda S, Santisopasri P, Murakami A, Kawanaka M, Sugiyama H, Gasquet M, Elias R, Balansard G, Ohigashi H (2002) In vitro anti-tumor promoting and anti-parasitic activities of the quassinoids from Eurycoma longifolia, a medicinal plant in Southeast Asia. J Ethnopharmacol 82:55–58
Kaewpiboon C, Lirdprapamongkol K, Srisomsap C, Winayanuwattikun P, Yongvanich T, Puwaprisirisan P, Svasti J, Assavalapsakul W (2012) Studies of the in vitro cytotoxic, antioxidant, lipase inhibitory and antimicrobial activities of selected Thai medicinal plants. BMC Complement Altern Med 12:1–8
Kardono LB, Angerhofer CK, Tsauri S, Padmawinata K, Pezzuto JM, Kinghorn AD (1991) Cytotoxic and antimalarial constituents of the roots of Eurycoma longifolia. J Nat Prod 54:1360–1367
Karuppusamy S (2009) A review on trends in production of secondary metabolites from higher plants by in vitro tissue, organ and cell cultures. J Med Plant Res 3:1222–1239
Khan S, Yu H, Li Q, Gao Y, Sallam BN, Wang H, Liu P, Jiang W (2019) Exogenous application of amino acids improves the growth and yield of lettuce by enhancing photosynthetic assimilation and nutrient availability. Agronomy 9:1–17
Kohlmeier M (2003) Nutrient metabolism. Academic Press, North Carolina
Kumari N, Varghese BA, Khan MA, Jangra S, Kumar A (2020) Abiotic elicitation: a tool for producing bioactive compounds. Plant Arch 20:2683–2689
Kuo PC, Damu AG, Lee KH, Wu TS (2004) Cytotoxic and antimalarial constituents from the roots of Eurycoma longifolia. Bioorg Med Chem 12:537–544
Li S, Peng F, Xiao Y, Gong Q, Bao Z, Li Y, Wu X (2020) Mechanisms of high concentration valine-mediated inhibition of peach tree shoot growth. Front Plant Sci 11:1–13
Li Y, Liang F, Jiang W, Yu F, Cao R, Ma Q, Dai X, Jiang J, Wang Y, Si S (2007) DH334, a beta-carboline anti-cancer drug, inhibits the CDK activity of budding yeast. Cancer Biol Ther 6:1193–1199
Low BS, Choi SB, Abdul Wahab H, Kumar Das P, Chan KL (2013) Eurycomanone, the major quassinoid in Eurycoma longifolia root extract increases spermatogenesis by inhibiting the activity of phosphodiesterase and aromatase in steroidogenesis. J Ethnopharmacol 149:201–207
Lulu T, Park SY, Ibrahim R, Paek KY (2015) Production of biomass and bioactive compounds from adventitious roots by optimization of culturing conditions of Eurycoma longifolia in balloon-type bubble bioreactor system. J Biosci Bioeng 119:712–717
Miyake K, Tezuka Y, Awale S, Li F, Kodata S (2010) Canthin-6-one alkaloids and a tirucallanoid from Eurycoma longifolia and their cytotoxic activity against ahuman HT-1080 fibrosarcoma cell line. Nat Prod Commun 5:17–22
Mohd NM, Ja’afar H, Zawawi DD, Alias N (2017) In vitro somatic embryos multiplication of Eurycoma longifolia Jack using temporary immersion system RITA®. Sains Malays 46:897–902
Mohnen D (2008) Pectin structure and biosynthesis. Curr Opin Plant Biol 11:266–277
Molnár Z, Virág E, Ördög V (2011) Natural substances in tissue culture media of higher plants. Acta Biol Szeged 55:123–127
Murashige T, Skoog F (1962) A revised medium for rapid growth and bio assays with tobacco tissue cultures. Physiol Plant 15:473–497
Namdeo AG (2007) Plant cell elicitation for production of secondary metabolites: a review. Rev Lat Am Lit Arts 1:69–79
Padgett PE, Leonard RT (1996) Free amino acid levels and the regulation of nitrate uptake in maize cell suspension cultures. J Exp Bot 47:871–883
Parre E, Geitmann A (2005) Pectin and the role of the physical properties of the cell wall in pollen tube growth of Solanum chacoense. Planta 220:582–592
Prasad B, Chayapathy N, Gururaj HB, Kumar V, Giridhar P, Ravishankar GA (2006) Valine pathway is more crucial than phenyl propanoid pathway in regulating capsaicin biosynthesis in Capsicum frutescens Mill. Agric Food Chem 54:6660–6666
Putalun W, Luealon W, De-Eknamkul W, Tanaka H, Shoyama Y (2007) Improvement of artemisinin production by chitosan in hairy root cultures of Artemisia annua L. Biotechnol Lett 29:1143–1146
Razak MF, Aidoo KE (2011) Toxicity studies of Eurycoma longifolia Jack-based remedial products. Asian J Pharm Clin Res 4:23–27
Rehman SU, Choe K, Yoo HH (2016) Review on a traditional herbal medicine, Eurycoma longifolia Jack (Tongkat Ali): Its traditional uses, chemistry, evidence-based pharmacology and toxicology. Molecules 21:1–31
Ribas-Agustí A, Van Buggenhout S, Palmero P, Hendrickx M, Van Loey A (2014) Investigating the role of pectin in carrot cell wall changes during thermal processing: a microscopic approach. Innov Food Sci Emerg Technol 24:113–120
Rost TL, Reynolds T (1985) Reversal of chlorsulfuron-induced inhibition of mitotic entry by isoleucine and valine. Plant Physiol 77:481–482
Ruan J, Li Z, Zhang Y, Chen Y, Liu M, Han L, Zhang Y, Wang T (2019) Bioactive constituents from the roots of Eurycoma longifolia. Molecules 24:1–16
Simic SG, Tusevski O, Maury S, Delaunay A, Joseph C, Hagège D (2014) Effects of polysaccharide elicitors on secondary metabolite production and antioxidant response in Hypericum perforatum L. shoot cultures. Sci World J 2014:1–10
Simpson SD, Ashford DA, Harvey DJ, Bowles DJ (1998) Short chain oligogalacturonides induce ethylene production and expression of the gene encoding aminocyclopropane 1-carboxylic acid oxidase in tomato plants. Glycobiology 8:579–583
Siregar LAM, Chan LK, Boey PL (2003) Selection of cell source and the effect of Ph and MS macronutrients on biomass production in cell cultures of Tongjat Ali (Eurycoma longifolia Jack). J Plant Biotechnol 5:131–135
Siregar LAM, Chan LK, Boey PL (2009) Effects of medium constituents on growth and canthinone accumulation in cell suspension cultures of Eurycoma longifolia Jack. Hayati J Biosci 16:69–77
Tambi MMI, Imran MK (2010) Eurycoma longifolia Jack in managing idiopathic male infertility. Asian J Androl 12:376–380
Tan SY, Kwan LS, Hirata Y, Chan LK, Nagaoka Y, Uesato S (2020) Cytotoxic activity of cell suspension cultured and plant derived crude extracts of Tongkat Ali (Eurycoma longifolia Jack) against Human Cancer Cell Lines. Int J Therm Sci 7:1–10
Veerashree V, Anuradha CM, Kumar V (2012) Elicitor-enhanced production of gymnemic acid in cell suspension cultures of Gymnema sylvestre R. Br. Plant Cell Tiss Org Cult 108:27–35
Wan Hassan WNA, Zulkifli RM, Ahmad F, Yunus MAC (2015) Antioxidant and tyrosinase inhibition activities of Eurycoma longifolia and Swietenia macrophylla. J Appl Pharm Sci 5:6–10
Wiktorowska E, Długosz M, Janiszowska W (2010) Significant enhancement of oleanolic acid accumulation by biotic elicitors in cell suspension cultures of Calendula officinalis L. Enzym Microb Technol 46:14–20
Yusuf H, Mustofa WMA, Susidarti RA, Asih PBS, Suryawati S (2013) A new quassinoid of four isolated compounds from extract Eurycoma longifolia, Jack roots and their in-vitro antimalarial activity. Int J Res Pharm Sci 4:728–734
Zhao J, Davis LC, Verpoorte R (2005) Elicitor signal transduction leading to production of plant secondary metabolites. Biotechnol Adv 23:283–333
Acknowledgements
The authors wish to thank School of Biological Sciences, Universiti Sains Malaysia for facilities and resources for research, while for the studies conducted in Japan, thanks are given to Kansai University especially to the Faculty of Chemistry Materials and Bioengineering for facilities and resources during the research attachment of the first two authors. Appreciation is also given to Yayasan Khazanah, Malaysia, for its scholarship to the second author.
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Kwan, L.S., Tan, S.Y., Hirata, Y. et al. Biotic elicitation at different feeding time in cell suspension cultures of Eurycoma longifolia Jack, a valuable medicinal plant, for enhancement of cytotoxic activity of bioactive compounds against human colon cancer cell line. In Vitro Cell.Dev.Biol.-Plant 58, 15–27 (2022). https://doi.org/10.1007/s11627-021-10189-x
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DOI: https://doi.org/10.1007/s11627-021-10189-x