title: Biotechnological Approaches for Production of Anti-Cancerous Compounds Resveratrol, Podophyllotoxin and Zerumbone.
abstract: Secondary metabolites from numerous plant sources have been developed as anti- cancer reagents and compounds such as resveratrol, podophyllotoxin and zerumbone are of particular importance in this regard. Since their de novo chemical synthesis is both arduous and commercially expensive, there has been an impetus to develop viable, biotechnological methods of production. Accordingly, this review focuses on the recent developments in the field, highlighting the use of micropropagation, cell suspension cultures, callus cultures, hairy root cultures, recombinant microbes and genetically modified higher plants. Optimization of media and culture conditions, precursor feeding, immobilization and the use of chemical or physical elicitation in various protocols has led to an increase in resveratrol and podophyllotoxin production. Heterologous gene transformation of higher plants with stilbene synthase derived from Arachis hypogaea or Vitis vinifera lead to resveratrol production with the concomitant increase in resistance to plant pathogens. Interestingly, genetic transformation of Podophyllum hexandrum and Linum flavum with Agrobacterium rhizogenes resulted in Ri-T-DNA gene(s)-mediated enhancement of podophyllotoxin production. Zerumbone yields from tissue cultured plantlets or from suspension cultures are generally low and these methods require further optimization. In microbes lacking the native resveratrol or zerumbone biosynthesis pathway, metabolic engineering required not only the introduction of several genes of the pathway, but also precursor feeding and optimization of gene expression to increase their production. Data pertaining to safety and toxicity testing are needed prior to use of these sources of anti-cancer compounds in therapy.
authors.affiliation: Department of Genetics, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India.
authors.forename: Krishnadas
authors.initials: K
authors.lastname: Nandagopal
authors.affiliation: Department of Botany, Centre of Advanced Study, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India.
authors.forename: Mihir
authors.initials: M
authors.lastname: Halder
authors.affiliation: Centre of Biotechnology, Siksha O Anusandhan University; Bhubaneswar- 751003, Odisha, India.
authors.forename: Biswabhusan
authors.initials: B
authors.lastname: Dash
authors.affiliation: Centre of Biotechnology, Siksha O Anusandhan University; Bhubaneswar- 751003, Odisha, India.
authors.forename: Sanghamitra
authors.initials: S
authors.lastname: Nayak
authors.affiliation: Department of Botany, Centre of Advanced Study, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India.
authors.forename: Sumita
authors.initials: S
authors.lastname: Jha
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001419:Bacteria / Q000235:genetics; D001709:Biotechnology / Q000379:methods*; D002478:Cells, Cultured; D006801:Humans; D060847:Metabolic Engineering / Q000379:methods; D010944:Plants / Q000235:genetics; D011034:Podophyllotoxin / Q000096:biosynthesis*; D000077185:Resveratrol / Q000138:chemical synthesis*; D012717:Sesquiterpenes / Q000138:chemical synthesis*
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C403304:zerumbone; D011034:Podophyllotoxin; D000077185:Resveratrol
keywords: Resveratrol; anti-cancer agents; cell suspension
  culture; elicitation; hairy root culture; metabolic engineering; podophyllotoxin; zerumbone.