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Cambial Meristematic Cells: A Sustainable Platform for the Production of Plant-Derived Anticancer Drugs

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Biotechnology and Production of Anti-Cancer Compounds

Abstract

For centuries, man has looked toward nature as a means to ameliorate a plethora of health conditions. Natural products (NPs), in particular those from plants, have proven to be a vital source of pharmaceuticals as in the case of the well-established anticancer drug, paclitaxel and the emerging ginsenoside triterpenoids. However, plant sources of high-value NPs can often be slow growing and are rarely domesticated and the target molecules are typically found in only low concentrations. Numerous strategies have been implemented for the production of these high-value molecules, including natural harvest from the source plant, total chemical synthesis or semi-synthesis from a more abundant precursor. Currently, plant cell culture arguably offers the most sustainable, robust, controllable and environmentally friendly platform to produce NPs for the pharmaceutical industry. In this context, the isolation of cambial meristematic cells (CMCs) and their potential utility to produce key anticancer drugs may serve to overcome some of the limitations previously associated with production of pharmaceuticals from traditional dedifferentiated plant cells (DDCs).

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References

  • Ajikumar PK, Xiao W-H, Tyo KEJ, Wang Y, Simeon F, Leonard E et al (2010) Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli. Science 330(6000):70–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amin A, Gali-Muhtasib H, Ocker M, Schneider-Stock R (2009) Overview of major classes of plant-derived anticancer drugs. Int J Biomed Sci 5(1):1–11

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bhojwani SS, Dantu PK (2013) Production of industrial phytochemicals. In: Plant tissue culture: an introductory text, 1st ed. Springer India. pp 275–286

    Google Scholar 

  • Chankova SG, Dimova E, Dimitrova M, Bryant PE (2007) Induction of DNA double-strand breaks by zeocin in Chlamydomonas reinhardtii and the role of increased DNA double-strand breaks rejoining in the formation of an adaptive response. Radiat Environ Biophys 46(4):409–416

    Article  CAS  PubMed  Google Scholar 

  • Cragg GM, Newman DJ (2005) Plants as a source of anti-cancer agents. J Ethnopharmacol 100(1–2):72–79

    Article  CAS  PubMed  Google Scholar 

  • Cragg GM, Newman DJ (2013) Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 1830(6):3670–3695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cragg PGM, Boyd MR, Schepartz SA (1995) Pharmaceutical prospecting and the potential for pharmaceutical crops. Natural product drug discovery and development at the United States National Cancer Institute. Ann Mo Bot Gard 82:47–53

    Article  Google Scholar 

  • Cusido RM, Onrubia M, Sabater-Jara AB, Moyano E, Bonfill M, Goossens A et al (2014) A rational approach to improving the biotechnological production of taxanes in plant cell cultures of Taxus spp. Biotechnol Adv 32(6):1157–1167

    Article  CAS  PubMed  Google Scholar 

  • Davies KM, Deroles SC (2014) Prospects for the use of plant cell cultures in food biotechnology. Curr Opin Biotechnol 26:133–140

    Article  CAS  PubMed  Google Scholar 

  • DeJong JM, Liu Y, Bollon AP, Long RM, Jennewein S, Williams D et al (2006) Genetic engineering of taxol biosynthetic genes in Saccharomyces cerevisiae. Biotechnol Bioeng 93(5):212–224

    Article  CAS  PubMed  Google Scholar 

  • Dias DA, Urban S, Roessner U (2012) A historical overview of natural products in drug discovery. Metabolites 2(2):303–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Engels B, Dahm P, Jennewein S (2008) Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards taxol (paclitaxel) production. Metab Eng 10(3–4):201–206

    Article  CAS  PubMed  Google Scholar 

  • Expósito O, Bonfill M, Moyano E, Onrubia M, Mirjalili MH, Cusidó RM et al (2009) Biotechnological production of taxol and related taxoids: current state and prospects. Anti Cancer Agents Med Chem 9(1):109–121

    Article  Google Scholar 

  • Fiehn O (2002) Metabolomics—the link between genotypes and phenotypes. Plant Mol Biol 48(1–2):155–171

    Article  CAS  PubMed  Google Scholar 

  • Fisher K, Turner S (2007) PXY, a receptor-like kinase essential for maintaining polarity during plant vascular-tissue development. Curr Biol 17(12):1061–1066

    Article  CAS  PubMed  Google Scholar 

  • Frankenstein C, Eckstein D, Schmitt U (2005) The onset of cambium activity—a matter of agreement? Dendrochronologia 23(1):57–62

    Article  Google Scholar 

  • Fulcher N, Sablowski R (2009) Hypersensitivity to DNA damage in plant stem cell niches. Proc Natl Acad Sci U S A 106(49):20984–20988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grafi G, Ben-Meir H, Avivi Y, Moshe M, Dahan Y, Zemach A (2007) Histone methylation controls telomerase-independent telomere lengthening in cells undergoing dedifferentiation. Dev Biol 306(2):838–846

    Article  CAS  PubMed  Google Scholar 

  • Guo BH, Kai GY, Jin HB, Tang KX (2006) Taxol synthesis. Afr J Biotechnol 5:15–20

    CAS  Google Scholar 

  • He L, Jagtap PG, Kingston DGI, Shen H-J, Orr GA, Horwitz SB (2000) A common Pharmacophore for taxol and the Epothilones based on the biological activity of a taxane molecule lacking a C-13 side chain. Biochemistry 39(14):3972–3978

    Article  CAS  PubMed  Google Scholar 

  • Holton R, Somoza A, Kim C, Liang HB, Biediger F, Boatman RJ, Shindo PD, Smith M, Kim CC, First S (1994a) Total synthesis of taxol. 2. Completion of the C and D rings. J Am Chem Soc 116(4):1599–1600

    Article  CAS  Google Scholar 

  • Holton R, Somoza A, Kim C, Liang HB, Biediger F, Boatman RJ, Shindo PD, Smith M, Kim CC, First S (1994b) Total synthesis of taxol. 1. Functionalization of the B ring. J Am Chem Soc 116(4):1597–1598

    Article  CAS  Google Scholar 

  • Howat S, Park B, Oh IS, Jin Y-W, Lee E-K, Loake GJ (2014) Paclitaxel: biosynthesis, production and future prospects. New Biotechnol 31(3):242–245

    Article  CAS  Google Scholar 

  • Huang Q, Roessner CA, Croteau R, Scott AI (2001) Engineering Escherichia coli for the synthesis of taxadiene, a key intermediate in the biosynthesis of taxol. Bioorg Med Chem 9(9):2237–2242

    Article  CAS  PubMed  Google Scholar 

  • Joshi JB, Elias CB, Patole MS (1996) Role of hydrodynamic shear in the cultivation of animal, plant and microbial cells. Chem Eng J Biochem Eng J 62(2):121–141

    Article  CAS  Google Scholar 

  • Keum Y-S, Park K-K, Lee J-M, Chun K-S, Park JH, Lee SK et al (2000) Antioxidant and anti-tumor promoting activities of the methanol extract of heat-processed ginseng. Cancer Lett 150(1):41–48

    Article  CAS  PubMed  Google Scholar 

  • Kingston DGI (2000) Recent advances in the chemistry of taxol. J Nat Prod 63:726–734

    Article  CAS  PubMed  Google Scholar 

  • Kolewe ME, Gaurav V, Roberts SC (2008) Pharmaceutically active natural product synthesis and supply via plant cell culture technology. Mol Pharm 5(2):243–256

    Article  CAS  PubMed  Google Scholar 

  • Lee E-K, Jin Y-W, Park JH, Yoo YM, Hong SM, Amir R et al (2010) Cultured cambial meristematic cells as a source of plant natural products. Nat Biotechnol 28(11):1213–1217

    Article  CAS  PubMed  Google Scholar 

  • Leung KW, Wong AS-T (2010) Pharmacology of ginsenosides: a literature review. Chin Med 5:20

    Article  PubMed  PubMed Central  Google Scholar 

  • Malik S, Cusidó RM, Mirjalili MH, Moyano E, Palazón J, Bonfill M (2011) Production of the anticancer drug taxol in Taxus baccata suspension cultures: a review. Process Biochem 46(1):23–34

    Article  CAS  Google Scholar 

  • Malik S, Hossein Mirjalili M, Fett-Neto AG, Mazzafera P, Bonfill M (2012) Living between two worlds: two-phase culture systems for producing plant secondary metabolites. Crit Rev Biotechnol 33:1–22

    Article  PubMed  Google Scholar 

  • Manfredi JJ, Parness J, Horwitz SB (1982) Taxol binds to cellular microtubules. J Cell Biol 94:688–696

    Article  CAS  PubMed  Google Scholar 

  • Miresmailli S, Isman MB (2014) Botanical insecticides inspired by plant-herbivore chemical interactions. Trends Plant Sci 19(1):29–35

    Article  CAS  PubMed  Google Scholar 

  • Mirjalili N, Linden JC (1996) Methyl Jasmonate induced production of taxol in suspension cultures of Taxus cuspidata: ethylene interaction and induction models. Biotechnol Prog Am Chem Soc 12(1):110–118

    Article  CAS  Google Scholar 

  • Moon SH, Venkatesh J, Yu JW, Park SW (2015) Differential induction of meristematic stem cells of Catharanthus roseus and their characterization. Comp Rend Biol Acad Sci 338(11):745–756

    Article  Google Scholar 

  • Mountford PG (2010) The taxol® story–development of a green synthesis via plant cell fermentation. In: Green chemistry in the pharmaceutical industry, pp 145–160

    Google Scholar 

  • Naill MC, Roberts SC (2004) Preparation of single cells from aggregated Taxus suspension cultures for population analysis. Biotechnol Bioeng 86(7):817–826

    Article  CAS  PubMed  Google Scholar 

  • Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70(3):461–477

    Article  CAS  PubMed  Google Scholar 

  • Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75(3):311–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicolaou KC, Yang Z, Liu JJ, Ueno H, Nantermet PG, Guy RK et al (1994) Total synthesis of taxol. Nature 367(6464):630–634

    Article  CAS  PubMed  Google Scholar 

  • Nosov AM (2012) Application of cell technologies for production of plant-derived bioactive substances of plant origin. Appl Biochem Microbiol 48(7):609–624

    Article  CAS  Google Scholar 

  • Ochoa-Villarreal M, Howat S, Jang MO, Kim IS, Jin Y-W, Lee E-K et al (2015) Cambial meristematic cells: a platform for the production of plant natural products. New Biotechnol 32(6):581–587

    Article  CAS  Google Scholar 

  • Ochoa-Villarreal M, Howat S, Hong S, Jang MO, Jin Y-W, Lee E-K et al (2016) Plant cell culture strategies for the production of natural products. BMB Rep 49(3):149–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oksman-Caldentey K-M, Inzé D (2004) Plant cell factories in the post-genomic era: new ways to produce designer secondary metabolites. Trends Plant Sci 9(9):433–440

    Article  CAS  PubMed  Google Scholar 

  • Pasquali G, Porto DD, Fett-Neto AG (2006) Metabolic engineering of cell cultures versus whole plant complexity in production of bioactive monoterpene indole alkaloids: recent progress related to old dilemma. J Biosci Bioeng 101(4):287–296

    Article  CAS  PubMed  Google Scholar 

  • Patel RN (1998) Tour de paclitaxel: biocatalysis for semisynthesis. Annu Rev Microbiol 52:361–395

    Article  CAS  PubMed  Google Scholar 

  • Pauwels L, Inzé D, Goossens A (2009) Jasmonate-inducible gene: what does it mean? Trends Plant Sci 14(2):87–91

    Article  CAS  PubMed  Google Scholar 

  • Pi Y, Jiang K, Hou R, Gong Y, Lin J, Sun X et al (2010) Examination of camptothecin and 10-hydroxycamptothecin in Camptotheca acuminata plant and cell culture, and the affected yields under several cell culture treatments. Biocell 34(3):139–143

    PubMed  Google Scholar 

  • Rao SR, Ravishankar GA (2002) Plant cell cultures: chemical factories of secondary metabolites. Biotechnol Adv 20(2):101–153

    Article  CAS  PubMed  Google Scholar 

  • Roberts SC (2007) Production and engineering of terpenoids in plant cell culture. Nat Chem Biol 3(7):387–395

    Article  CAS  PubMed  Google Scholar 

  • Sabater-Jara AB, Tudela LR, López-Pérez AJ (2010) In vitro culture of Taxus sp.: strategies to increase cell growth and taxoid production. Phytochem Rev 9(2):343–356

    Article  CAS  Google Scholar 

  • Schiff PB, Horwitz SB (1980) Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci U S A 77(3):1561–1565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strobel GA, Stierle A, Hess WM (1993) Taxol formation in yew—Taxus. Plant Sci 92(1):1–12

    Article  CAS  Google Scholar 

  • Sugimoto K, Jiao Y, Meyerowitz EM (2010) Arabidopsis regeneration from multiple tissues occurs via a root development pathway. Dev Cell 18(3):463–471

    Article  CAS  PubMed  Google Scholar 

  • Tabata H (2006) Production of paclitaxel and the related taxanes by cell suspension cultures of Taxus species. Curr Drug Targets 7(4):453–461

    Article  CAS  PubMed  Google Scholar 

  • Thorpe T (2012) History of plant cell culture. In: Loyola-Vargas VM, Ochoa-Alejo N (eds) Methods in molecular biology, vol 877. Humana Press, Totowa, NJ, pp 169–180

    Google Scholar 

  • Vongpaseuth K, Roberts SC (2007) Advancements in the understanding of paclitaxel metabolism in tissue culture. Curr Pharm Biotechnol 8(4):219–236

    Article  CAS  PubMed  Google Scholar 

  • Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT (1971) Plant antitumor agents. VI. Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 93(9):2325–2327

    Article  CAS  PubMed  Google Scholar 

  • Wilson SA, Roberts SC (2012) Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules. Plant Biotechnol J 10(3):249–268

    Article  CAS  PubMed  Google Scholar 

  • Wilson SA, Roberts SC (2014) Metabolic engineering approaches for production of biochemicals in food and medicinal plants. Curr Opin Biotechnol 26:174–182

    Article  CAS  PubMed  Google Scholar 

  • Wu S, Chappell J (2008) Metabolic engineering of natural products in plants; tools of the trade and challenges for the future. Curr Opin Biotechnol 19(2):145–152

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Ge X, Dolan MC (2011) Towards high-yield production of pharmaceutical proteins with plant cell suspension cultures. Biotechnol Adv 29(3):278–299

    Article  CAS  PubMed  Google Scholar 

  • Ye Z-H (2002) Vascular tissue differentiation and pattern formation in plants. Annu Rev Plant Biol 53:183–202

    Article  CAS  PubMed  Google Scholar 

  • Yokoshima S, Ueda T, Kobayashi S, Sato A, Kuboyama T, Tokuyama H et al (2002) Stereocontrolled total synthesis of (+)-vinblastine. J Am Chem Soc 124(10):2137–2139

    Article  CAS  PubMed  Google Scholar 

  • Yousefzadi M, Sharifi M, Behmanesh M, Moyano E, Bonfill M, Cusido RM et al (2010) Podophyllotoxin: current approaches to its biotechnological production and future challenges. Eng Life Sci 10(4):281–292

    Article  CAS  Google Scholar 

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Acknowledgments

M.O.V. is supported by a scholarship from CONACYT, Mexico.

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Correspondence to Marisol Ochoa-Villarreal .

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Loake, V.I.P., Ochoa-Villarreal, M. (2017). Cambial Meristematic Cells: A Sustainable Platform for the Production of Plant-Derived Anticancer Drugs. In: Malik, S. (eds) Biotechnology and Production of Anti-Cancer Compounds . Springer, Cham. https://doi.org/10.1007/978-3-319-53880-8_6

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