Revista Mexicana de I ngeniería Q uímica CONTENIDO Interest of cellular di ff erentiation in the production of vincristine and vinblastine in suspension cultures of Catharanthus roseus (L.) G Don.

Plant cell culture technology, particularly suspension cultures, appears as a convenient tool to industrially produce molecules such as the anticancer molecules vincristine and vinblastine. Cell di ff erentiation is needed for their in vivo synthesis and thus in vitro cultures have usually been considered as limited producing platforms. Several studies have recently detected vincristine and vinblastine in early di ff erentiated calluses and also in suspension cultures. Nevertheless, the degree of cell di ff erentiation has not been addressed, particularly in suspension cultures that could be used as a large-scale producing platform. Therefore, the e ff ect of culture conditions on the production of vincristine and vinblastine, taking into account cytodi ff erentiation within cell aggregates, has been analyzed for the first time. Culture conditions such as light exposure and plant growth regulator regimes have been shown to a ff ect cell di ff erentiation. Moreover, cell di ff erentiation was observed to be closely related to vincristine and vinblastine titers. Results provide important clues into the comprehension of in vitro culture performance for metabolites production requiring in vivo cell di ff erentiation. They demonstrated the utility of taking into account cell di ff erentiation for the further development of novel advanced processes of di ff erentiated cell suspension cultures for producing valuable molecules, including biological medicines such as vincristine and vinblastine.

[1]  A. Marc,et al.  In situ cell differentiation monitoring of Catharanthus roseus suspension culture processes by NIR spectroscopy , 2019, Bioprocess and Biosystems Engineering.

[2]  A. Kaleem,et al.  Application of response surface methodology for statistical optimization of carboxymethylcellulase by Thermomyces dupontii TK-19 using submerged fermentation , 2019, Revista Mexicana de Ingeniería Química.

[3]  O. Safonova,et al.  Completion of the canonical pathway for assembly of anticancer drugs vincristine/vinblastine in Catharanthus roseus , 2018, The Plant journal : for cell and molecular biology.

[4]  G. Agati,et al.  Ficus carica L. leaf anatomy: Trichomes and solid inclusions , 2019 .

[5]  R. Wise,et al.  Plant Anatomy: A Concept-Based Approach to the Structure of Seed Plants , 2018, Springer International Publishing.

[6]  Sumaryono,et al.  Cinchona cells performance in in vitro culture: quinine alkaloid production with application of different elicitors , 2018, IOP Conference Series: Earth and Environmental Science.

[7]  J. Al-Sabahi,et al.  Potentiating biosynthesis of the anticancer alkaloids vincristine and vinblastine in callus cultures of Catharanthus roseus , 2018 .

[8]  Md. Akhlaquer Rahman,et al.  Agricultural, Pharmaceutical, and Therapeutic Interior of Catharanthus roseus (L.) G. Don , 2017 .

[9]  M. M. Khan,et al.  Vincristine and Vinblastine Anticancer Catharanthus Alkaloids: Pharmacological Applications and Strategies for Yield Improvement , 2017 .

[10]  I. Iriawati,et al.  Vinblastine and Vincristine Production on Madagascar Periwinkle (Catharanthus roseus (L.) G. Don) Callus Culture Treated with Polethylene Glycol , 2016 .

[11]  N. Christodoulakis,et al.  Leaf Tissue Arrangement , Preliminary Phytochemical Investigation and Callus Induction from the Medicinal Hemi-parasite Osyris alba , 2016 .

[12]  Jiachen Zi,et al.  Effects of Adding Vindoline and MeJA on Production of Vincristine and Vinblastine, and Transcription of their Biosynthetic Genes in the Cultured CMCs of Catharanthus roseus , 2015, Natural product communications.

[13]  Jianhua Zhu,et al.  Biosynthesis and regulation of terpenoid indole alkaloids in Catharanthus roseus , 2015, Pharmacognosy reviews.

[14]  S. Bhatia,et al.  Technical Glitches in Micropropagation , 2015 .

[15]  C. Walter,et al.  Formation of plant tracheary elements in vitro – a review , 2014, New Zealand Journal of Forestry Science.

[16]  Kayghobad Shams,et al.  In Vitro Studies on Egyptian Catharanthus roseus (L.) G.Don V: Impact of Stirred Reactor Physical Factors on Achievement of Cells Proliferation and Vincristine and Vinblastine Accumulation , 2014 .

[17]  Susan C. Roberts,et al.  Implications of Cellular Heterogeneity on Plant Cell Culture Performance , 2013 .

[18]  S. O’Connor,et al.  A virus-induced gene silencing approach to understanding alkaloid metabolism in Catharanthus roseus. , 2011, Phytochemistry.

[19]  C. Kalidass,et al.  EFFECT OF AUXIN AND CYTOKININ ON VINCRISTINE PRODUCTION BY CALLUS CULTURES OF Catharanthus roseus L. (APOCYNACEAE) , 2010 .

[20]  Kexuan Tang,et al.  Effect of plant growth regulators on the biosynthesis of vinblastine, vindoline and catharanthine in Catharanthus roseus , 2010, Plant Growth Regulation.

[21]  A. Majd,et al.  High in vitro production of ant-canceric indole alkaloids from periwinkle ( Catharanthus roseus) tissue culture , 2008 .

[22]  A. Srivastava,et al.  Influence of gibberellic acid on 14CO2 metabolism, growth, and production of alkaloids in Catharanthus roseus , 2007, Photosynthetica.

[23]  D. Singh,et al.  Simultaneous determination of vincristine, vinblastine, catharanthine, and vindoline in leaves of catharanthus roseus by high-performance liquid chromatography. , 2005, Journal of chromatographic science.

[24]  R. Savidge The role of plant hormones in higher plant cellular differentiation. II. Experiments with the vascular cambium, and sclereid and tracheid differentiation in the pine,Pinus contorta , 1983, The Histochemical Journal.

[25]  V. Burlat,et al.  Co-expression of three MEP pathway genes and geraniol 10-hydroxylase in internal phloem parenchyma of Catharanthus roseus implicates multicellular translocation of intermediates during the biosynthesis of monoterpene indole alkaloids and isoprenoid-derived primary metabolites. , 2004, The Plant journal : for cell and molecular biology.

[26]  S. Kwak,et al.  Relationship between cell morphology and indole alkaloid production in suspension cultures of Catharanthus roseus , 1994, Plant Cell Reports.

[27]  S. Kwak,et al.  High frequency plant regeneration from anther-derived cell suspension cultures via somatic embryogenesis in Catharanthus roseus , 1994, Plant Cell Reports.

[28]  R. Verpoorte,et al.  Effect of auxin on cytodifferentiation and production of quinoline alkaloids in compact globular structures of Cinchona ledgeriana , 1990, Plant Cell Reports.

[29]  R. Tyler,et al.  Photoautotrophic cell suspension cultures of periwinkle (Catharanthus roseus (L.) G. Don): Transition from heterotrophic to photoautotrophic growth , 1986, Plant Cell Reports.

[30]  M. Jolicoeur,et al.  Screening of Catharanthus roseus secondary metabolites by high-performance liquid chromatography. , 2002, Journal of chromatography. A.

[31]  A. Gravot,et al.  Production of plant secondary metabolites: a historical perspective , 2001 .

[32]  F. Vázquez-Flota,et al.  Multicellular Compartmentation of Catharanthus roseus Alkaloid Biosynthesis Predicts Intercellular Translocation of a Pathway Intermediate , 1999, Plant Cell.

[33]  O. Gamborg,et al.  Plant Cell, Tissue and Organ Culture , 1995, Springer Lab Manual.

[34]  M. Sugiyama,et al.  Mechanisms of the proliferation and differentiation of plant cells in cell culture systems. , 1994, The International journal of developmental biology.

[35]  C. Haigler,et al.  Cell Expansion and Tracheary Element Differentiation Are Regulated by Extracellular pH in Mesophyll Cultures of Zinnia elegans L , 1994, Plant physiology.

[36]  R. Verpoorte,et al.  PLANT CELL BIOTECHNOLOGY FOR THE PRODUCTION OF ALKALOIDS: PRESENT STATUS AND PROSPECTS' , 1993 .

[37]  J. Mauseth Botany : An Introduction to Plant Biology , 1991 .

[38]  V. Kauppinen,et al.  Mass Spectral Evidence of the Occurrence of Vindoline in Heterotrophic Cultures of Catharanthus roseus Cells. , 1989, Planta medica.

[39]  A. Cutler,et al.  Subcellular Localization of Enzymes Involved in Indole Alkaloid Biosynthesis in Catharanthus roseus. , 1987, Plant physiology.

[40]  R. Hall,et al.  Intercellular and Intercultural Heterogeneity in Secondary Metabolite Accumulation in Cultures of Catharanthus roseus following Cell Line Selection , 1987 .

[41]  N. Kurano,et al.  Isolation of vinblastine in callus culture with differentiated roots of catharanthus roseus (L). g. don , 1987 .

[42]  M. Zenk,et al.  Instability of Indole Alkaloid Production in Catharanthus roseus Cell Suspension Cultures , 1984, Planta medica.

[43]  K. Lindsey,et al.  The Relationship between Growth Rate, Differentiation and Alkaloid Accumulation in Cell Cultures , 1983 .

[44]  G. Krauss,et al.  Indole Alkaloid Formation and Storage in Cell Suspension Cultures of Catharanthus roseus , 1983, Planta medica.

[45]  K. Knobloch,et al.  Medium- and light-induced formation of serpentine and anthocyanins in cell suspension cultures of Catharanthus roseus , 1982 .

[46]  A. Scott,et al.  Formation of catharanthine, akuammicine and vindoline in Catharanthus roseus suspension cells , 1980 .

[47]  P. Mahlberg,et al.  REACTIONS OF ALKALOID AND HISTOCHEMICAL INDICATORS IN LATICIFERS AND SPECIALIZED PARENCHYMA CELLS OF CATHARANTHUS ROSEUS (APOCYNACEAE) , 1976 .