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Production of camptothecin in the elicited callus cultures of Nothapodytes nimmoniana (J. Graham) Mabberly

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Abstract

The biotechnological approach of in vitro cultures elicitation offers an alternative strategy for the production of camptothecin (CPT) in Nothapodytes nimmoniana to mitigate indiscriminate harvest of the endangered natural population for the alkaloid. Yeast extract (YE) and vanadyl sulfate (VS) elicitors were used to enhance the biosynthesis of CPT in hypocotyl-derived callus cultures of N. nimmoniana by cultivation using solid and liquid Murashige and Skoog (MS) medium amended with NAA + BAP (2.0 + 1.0 mg L−1). Effects of the two elicitors on biomass and CPT production at 6.25, 12.5, 25, 50 and 75 mg L−1 concentrations using callus cultures from three cell lines were evaluated after 15, 30 and 45 days culture. Yeast extract elicitor treatments showed a linear enhancement effect on biomass and CPT production up to 50 mg L−1 YE and beyond the concentrations, no significant effect was observed. Enhanced biomass and CPT production were achieved with VS elicitor up to 25 mg L−1 concentrations but, 50 and 75 mg L−1 VS had minimal effects on biomass and CPT production in callus sources and incubation duration-dependent manner. The intracellular yield of CPT in liquid media-cultivated cultures at concentrations of the two elicitors was lower when compared to solid media treatments relative control due to the extracellular accumulation but, higher overall production. Accumulation of the biomass showed association with produced CPT in the elicitor treatments and control cultures.

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References

  • Abraham F, Bhatt A, Keng CL, Indrayanto G, Sulaiman SF (2011) Effect of yeast extract and chitosan on shoot proliferation, morphology and antioxidant activity of Curcuma mangga in vitro plantlets. Afr J Biotechnol 10(40):7787–7795. doi:10.5897/AJB10.1261

    Article  CAS  Google Scholar 

  • Bhagwath SG, Hjortso MA (2000) Statistical analysis of elicitation strategies for thiarubrine A production in hairy root cultures of Ambrosia artemisiifolia. J Biotechnol 80(2):159–167. doi:10.1016/S0168-1656(00)00256-X

    Article  CAS  Google Scholar 

  • Boller T (1995) Chemo-perception of microbial signals in plant cells. Ann Rev Plant Physiol Plant Mol Biol 46:189–214. doi:10.1146/annurev.pp.46.060195.001201

    Article  CAS  Google Scholar 

  • Bonfill M, Palazon J, Cusido RM et al (2003) Influence of elicitors on taxane production and 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity in the Taxus media cells. Plant Physiol 108:1171–1178. doi:10.1016/S0981-9428(02)00013-X

    Google Scholar 

  • Chen H, Chen F (2000) Effects of yeast elicitor on the growth and secondary metabolism of a high-tanshinone-producing line of the Ti-transformed Salvia miltiorrhiza cells in suspension culture. Process Biochem 35(8):837–840. doi:10.1016/S0032-9592(99)00146-6

    Article  CAS  Google Scholar 

  • Chuntaratin P (2006) Production of plumbagin by hairy root, callus, and cell suspension cultures of Plumbago indica L. A Thesis submitted to graduate school, Kasetsart University, ISBN 974-16-2187-6, pp 97

  • Ciddi V, Shuler ML (2000) Camptothecin from callus cultures of Nothapodytes foetida. Biotechnol Lett 22(2):129–132. doi:10.1023/A:1005666223003

    Article  CAS  Google Scholar 

  • Clements MK, Jone CB, Cumming M, Daud SS (1999) Antiangiogenic potential of camptothecin and topotecan. Cancer Chemother Pharmacol 44:411–416. doi:10.1007/s002800050997

    Article  CAS  Google Scholar 

  • Dandin VS, Murthy HN (2012) Enhanced in vitro multiplication of Nothapodytes nimmoniana Graham using semi-solid and liquid cultures and estimation of camptothecin in the regenerated plants. Acta Physiol Plant 34:1381–1386. doi:10.1007/s11738-012-0934-x

    Article  CAS  Google Scholar 

  • Fulzele DP, Satdive RK (2005) Comparison of techniques for the extraction of the anti-cancer drug camptothecin from Nothapodytes foetida. J Chromatogr Anal 1063(2):9–13. doi:10.1016/j.chroma.2004.11.020

    Article  CAS  Google Scholar 

  • Fulzele DP, Satdive RK, Pol BB (2001) Growth and production of camptothecin by cell suspension cultures of Nothapodytes foetida. Planta Med 67(2):150–152. doi:10.1055/s-2001-11519

    Article  CAS  Google Scholar 

  • Furmanowa M, Olędzka H, Sykłowska-Baranek K et al (2000) Increased taxane accumulation in callus cultures of Taxus cuspidata and Taxus × media by some elicitors and precursors. Biotechnol Lett 22(18):1449–1452. doi:10.1023/A:1005611114628

    Article  CAS  Google Scholar 

  • Govindachari TR, Viswanathan N (1972) Alkaloids of Mappia foetida. Phytochem 11(12):3529. doi:10.1016/S0031-9422(00)89852-0

    Article  CAS  Google Scholar 

  • Hahn MG, Albersheim P (1978) Host–pathogen interactions. Plant Physiol 62:107–111. doi:10.1104/pp.68.5.1161

    Article  CAS  Google Scholar 

  • Hakkim FL, Kalyani S, Essa M et al (2011) Production of rosmarinic in Ocimum sanctum cell cultures by the influence of sucrose, phenylalanine, yeast extract, and methyl jasmonate. Int J Biol Med Res 2:1070–1074

    Google Scholar 

  • Holden MA, Holden PR, Yeoman MM (1988) Elicitation of cell cultures. Manipulating secondary metabolism in culture. Cambridge University Press, Cambridge, pp 57–65

    Google Scholar 

  • Hong MLK, Bhatt A, Ping NS, Keng CL (2012) Detection of elicitation effect on Hyoscyamus niger L. root cultures for the root growth and production of tropane alkaloids. Romanian Biotechnol Lett 17(3):7341

    Google Scholar 

  • Hussain MS, Fareed S, Ansari S et al (2012) Current approaches toward the production of plant secondary metabolites. J Pharm BioAllied Sci 4:10–20. doi:10.4103/0975-7406.92725

    Article  Google Scholar 

  • Isah T (2016) Induction of somatic embryogenesis in woody plants. Acta Physiol Plant 38:118. doi:10.1007/s11738-016-2134-6

    Article  Google Scholar 

  • Isah T, Mujib A (2015a) In vitro propagation and camptothecin production in Nothapodytes nimmoniana. Plant Cell Tiss Organ Cult 121:1–10. doi:10.1007/s11240-014-0683-1

    Article  CAS  Google Scholar 

  • Isah T, Mujib A (2015b) Camptothecin from Nothapodytes nimmoniana: review on biotechnology applications. Acta Physiol Plant 37:106. doi:10.1007/s11738-015-1854-3

    Article  Google Scholar 

  • Isah T, Mujib A (2015c) Enhanced in vitro seedling recovery in Nothapodytes nimmoniana. Brit Biotechnol J 6(1):2231–2927. doi:10.9734/bbj/2015/15368

    Article  Google Scholar 

  • Jaisi A, Panichayupakaranant P (2016) Increased production of plumbagin in Plumbago indica root cultures by biotic and abiotic elicitors. Biotechnol Lett 38:351–355. doi:10.1007/s10529-015-1969-z

    Article  CAS  Google Scholar 

  • Jartoodeh SV, Davarynejad GH, Tehranifar A, Kaveh H, Bisheh HA (2013) Reducing browning problem in micropropagation of three pear cultivars; Sebri, Shekari and Natanz. Curr Opin Agric 2(1):25

    Google Scholar 

  • Jisha KG (2006) A study on the production of camptothecin from Ophiorrhiza mungos and Nothapodytes foetida using cell and tissue culture. Thesis submitted to Mahatma Gandhi Univ. Through Amala Cancer Res Centre, Thrissur, in partial fulfillment of the requirements for the award of Doctor of Philosophy

  • Kai G, Wu C, Gen L et al (2015) Biosynthesis and biotechnological production of anti-cancer drug camptothecin. Phytochem Rev 14(3):525–539. doi:10.1007/s11101-015-9405-5

    Article  CAS  Google Scholar 

  • Kargi F, Potts P (1991) Effect of various stress factors on indole alkaloid formation by Catharanthus roseus (periwinkle) cells. Enzyme Microb Technol 13(9):760–763. doi:10.1016/0141-0229(91)90056-G

    Article  CAS  Google Scholar 

  • Karwasara VS, Dixit VK (2013) Culture medium optimization for camptothecin production in cell suspension cultures of Nothapodytes nimmoniana (J. Grah.) Mabb. Plant Biotechnol Rep 12:1–13. doi:10.1007/s11816-012-0270-z

    Google Scholar 

  • Kedari P, Malpathak N (2013) Subcellular localization and quantification of camptothecin in different plant parts of Chonemorpha fragrans. Adv Zool Bot 1:34–38. doi:10.13189/azb.2013.010203

    CAS  Google Scholar 

  • Kulkarni AV, Patwardhan AA, Lele U, Malpathak NP (2010) Production of camptothecin in cultures of Chonemorpha grandiflora. Pharmacogn Res 2(5):296–299. doi:10.4103/0974-8490.72327

    Article  CAS  Google Scholar 

  • Kümmritz S, Louis M, Haas C et al (2016) Fungal elicitors combined with a sucrose feed significantly enhance triterpene production of a Salvia fruticosa cell suspension. Appl Microbiol Biotechnol 100(16):7071–7082. doi:10.1007/s00253-016-7432-9

    Article  Google Scholar 

  • Lee-Parsons CW, Ertürk S, Tengtrakool J (2004) Enhancement of ajmalicine production in Catharanthus roseus cell cultures with methyl jasmonate is dependent on timing and dosage of elicitation. Biotechnol Lett 26(20):1595–1599. doi:10.1023/B:BILE.0000045825.37395.94

    Article  CAS  Google Scholar 

  • Li S, Zhang W, Nothrup K, Zhang D (2014) Distribution of the Camptotheca decaisne: an endangered status. Pharma Crops 5:135–139. doi:10.2174/2210290601405010135

    Article  Google Scholar 

  • Lindsey K (1985) Manipulation by the nutrient limitation of the biosynthetic activity of immobilized cells of Capsicum frutescens Mill. ev. annuum. Planta 165:126–133. doi:10.1007/BF00392221

    Article  CAS  Google Scholar 

  • Liu YQ, Li WQ, Morris-Natschke SL et al (2015) Perspectives on biologically active camptothecin derivatives. Med Res Rev 35:753–789. doi:10.1002/med.21342

    Article  Google Scholar 

  • Loc N, Giang N (2012) Effects of elicitors on the enhancement of asiaticoside biosynthesis in cell cultures of centella (Centella asiatica L. Urban). Chem Pap 66(7):642–648. doi:10.2478/s11696-012-0168-9

    Article  CAS  Google Scholar 

  • Loc NH, Anh NHT, Khuyen LTM et al (2014) Effects of yeast extract and methyl jasmonate on the enhancement of solasodine biosynthesis in cell cultures of Solanum hainanense Hance. J BioSci Biotechnol 3(1):1–6

    Google Scholar 

  • Malik SS, Laura JS (2014) Distribution of camptothecin through the plant kingdom. Int J Curr Res 6(5):6497–6507

    Google Scholar 

  • Matkowski A (2008) Plant in vitro culture for the production of antioxidants—a review. Biotechnol Adv 26:548–560. doi:10.1016/j.biotechadv.2008.07.001

    Article  CAS  Google Scholar 

  • Murashige T, Skoog F (1962) A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol Plant 15(3):473–497. doi:10.1111/j.1399-3054.1962.tb08052.x

    Article  CAS  Google Scholar 

  • Murthy HN, Lee EJ, Paek KY (2014) Production of secondary metabolites from cell and organ cultures: strategies and approaches for biomass improvement and metabolite accumulation. Plant Cell Tiss Organ Cult 118(1):1–16. doi:10.1007/s11240-014-0467-7

    Article  CAS  Google Scholar 

  • Onrubia M, Moyano E, Bonfill M et al (2010) An approach to the molecular mechanism of methyl jasmonate and vanadyl sulfate elicitation in Taxus baccata cell cultures: the role of txs and bapt gene expression. Biochem Eng J 53(1):104–111. doi:10.1016/j.bej.2010.10.001

    Article  CAS  Google Scholar 

  • Palazon J, Cusido RM, Bonfill M et al (2003) Elicitation of different Panax ginseng transformed root phenotypes for an improved ginsenoside production. Plant Physiol Biochem 41(11):1019–1025. doi:10.1016/j.plaphy.2003.09.002

    Article  CAS  Google Scholar 

  • Patra N, Srivastava AK (2014) Enhanced production of artemisinin by hairy root cultivation of Artemisia annua in a modified stirred tank reactor. Appl Biochem Biotechnol 174(6):2209–2222. doi:10.1007/s12010-014-1176-8

    Article  CAS  Google Scholar 

  • Rahpeyma SA, Moieni A, Javaran JM (2015) Paclitaxel production is enhanced in the suspension-cultured Corylus avellana cells by using combinations of sugar, precursor, and elicitor. Eng Life Sci 15(2):234–242. doi:10.1002/elsc.201400115

    Article  CAS  Google Scholar 

  • Ramesha BT, Amna T, Ravikanth G et al (2008) Prospecting for the camptothecines from Nothapodytes nimmoniana in Western Ghats, South India: identification of high-yielding sources of camptothecin and new families of camptothecines. J Chromatogr Sci 46(4):362–368. doi:10.1093/chromsci/46.4.362

    Article  CAS  Google Scholar 

  • Ravikumar K, Ved DK (2000) 100 red-listed medicinal plants of conservation concern in South India, 1st edn. FRLHT, Bangalore

    Google Scholar 

  • Saco D, Martin S, San Jose P (2013) Vanadium distribution in roots and leaves of Phaseolus vulgaris: morphological and ultrastructural effects. Biol Plant 57(1):128–132. doi:10.1007/s10535-012-0133-z

    Article  CAS  Google Scholar 

  • Saito K, Sudo H, Yamazaki M et al (2001) Feasible production of camptothecin by hairy root culture of Ophiorrhriza pumila. Plant Cell Rep 20:267–271. doi:10.1007/s002990100320

    Article  CAS  Google Scholar 

  • Sanchez-Sampedro MA, Fernandez-Tarrago J, Corchete P (2005) Yeast extract and methyl jasmonate-induced silymarin production in cell cultures of Silybum marianum (L.) Gaernt. J Biotechnol 119:60–69. doi:10.1016/j.jbiotec.2005.06.012

    Article  CAS  Google Scholar 

  • Smith JI, Smart NJ, Misawa M et al (1987) Increased accumulation of indole alkaloids by some cell lines of Catharanthus roseus in response to the addition of vanadyl sulfate. Plant Cell Rep 6(2):142–145. doi:10.1007/BF00276673

    CAS  Google Scholar 

  • Sriram D, Yogeeswar P, Thirumurugan R, Bal TR (2005) Camptothecin and its analogs: a review on their chemotherapeutic potential. Nat Products Res 19(4):393–412. doi:10.1080/14786410412331299005

    Article  CAS  Google Scholar 

  • Srivastava V, Negi AS, Kumar JK et al (2005) Plant-based anticancer molecules: a chemical and biological profile of some important leads. Bioorganic Med Chem 13:5892–5908. doi:10.1016/j.bmc.2005.05.066

    Article  CAS  Google Scholar 

  • Tallevi S, DiCosmo F (1988) Stimulation of indole alkaloid content in vanadium treated Catharanthus roseus suspension cultures. Planta Med 54:149–152. doi:10.1055/s-2006-962374

    Article  CAS  Google Scholar 

  • Uday Bhanu M, Kondap AK (2010) Neurotoxic activity of a topoisomerase-I inhibitor, camptothecin in cultured cerebellar granule neurons. Neurotoxicol 31:730–737. doi:10.1016/j.neuro.2010.06.008

    Article  CAS  Google Scholar 

  • Vanisree M, Tsay HS (2004) Plant cell cultures—an alternative and efficient source for the production of biologically important secondary metabolites. Int J Appl Sci Eng 2:29–43

    Google Scholar 

  • Verpoorte R, Contin A, Memelink J (2002) Biotechnology for the production of plant secondary metabolites. Phytochem Rev 1:13–25. doi:10.1023/A:1015871916833

    Article  CAS  Google Scholar 

  • Wall ME, Wani MC, Cook CE et al (1966) Plant antitumor agents I: the isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J Am Chem Soc 88:3888–3890. doi:10.1021/ja00968a057

    Article  CAS  Google Scholar 

  • Yamazaki Y, Sudo H, Yamazaki M et al (2003) Camptothecin biosynthetic genes in the hairy roots of Ophiorrhiza pumila: cloning, characterization, and differential expression in tissues and by stress compounds. Plant Cell Physiol 44(4):395–403. doi:10.1093/pcp/pcg051

    Article  CAS  Google Scholar 

  • Yan Q, Hu ZD, Wu JY (2006) Synergistic effects of biotic and abiotic elicitors on the production of tanshinones in Salvia miltiorrhiza hairy root culture. China J Chin Materia Med 31(3):188–191. doi:10.1007/s00253-007-1332-y

    CAS  Google Scholar 

  • Zhao JL, Zhou LG, Wu JY (2010) Effects of biotic and abiotic elicitors on cell growth and tanshinone accumulation in Salvia miltiorrhiza cell cultures. Appl Microbiol Biotechnol 87(1):137–144. doi:10.1007/s00253-010-2443-4

    Article  CAS  Google Scholar 

  • Zheng Z, Wu M (2004) Cadmium treatment enhances the production of alkaloid secondary metabolites of Catharanthus roseus. Plant Sci 166:507–514. doi:10.1016/j.plantsci.2003.10.022

    Article  CAS  Google Scholar 

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Acknowledgements

This work was financially supported by the agreed terms between Department of Biotechnology, Government of India New Delhi and The World Academy of Sciences for the Advancement of Science in Developing Countries (TWAS) Trieste Italy, through DBT–TWAS Postgraduate Research Fellowship. I am highly grateful to Hamdard University New Delhi, India for providing research facilities.

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  1. Cellular Differentiation and Molecular Genetics Section, Department of Botany, Hamdard University, New Delhi, 110 062, India

    Tasiu Isah

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Isah, T. Production of camptothecin in the elicited callus cultures of Nothapodytes nimmoniana (J. Graham) Mabberly. Chem. Pap. 71, 1091–1106 (2017). https://doi.org/10.1007/s11696-016-0056-9

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