Cell Suspension and In Vitro Production of Colchicine in Wild Colchicum Hierosolymitanum Feib

Abstract

In the era of personalized medicine, pharmaceutical companies are actively seeking partners to develop Companion diagnostics. Common choices of partners include large diagnostic manufacturers and traditional Contract Research Organizations (CROs), neither of which provides an entire solution. Diagnostics companies have an intrinsic bias toward internal product lines, and are therefore incentivized to direct diagnostics development toward an existing technology platform. The expertise of a CRO lies in the monitoring of pharmaceutical programs, not in diagnostics. In addition, few traditional partners have significant clinical laboratory experience or offer accredited clinical laboratories to ensure that the diagnostic clinical trials are designed for, and conducted in, laboratories that meet regulatory standards. Lastly, these organizations are inexperienced in managing and coordinating the multiple partners required in the development process. The Contract Diagnostics Organization (CDO) is a new concept designed to aid pharmaceutical companies in addressing challenges in companion diagnostics development. This business model provides pharmaceutical companies a complete outsourcing partner to initiate and manage the parallel development of companion diagnostic tests in synergy with drug development. The CDO combines all of the necessary services, including diagnostics research, an accredited clinical laboratory, project management and regulatory, manufacturing, and consulting in an integrated, technology-independent manner. Thus, the CDO focuses on its pharmaceutical partner's business objectives and ensures the speediest path to market a valuable, personalized drug for patients.

Colchicine Quantification in Salt Stress Treated Culture of Colchicum luteum Baker by High Pressure Liquid Chromatography

“…Earlier, in a similar approach Al-Fayyad et al (29) quantified colchicine yield in corms (0.052%), flowers (0.025%) and leaves (0.013%) in Colchicum hierosolymitanum by using different NPK fertilizer levels. In this species (C. hierosolymitanum), the maximum yield of colchicine was also noted in callus added to 30 mM NH 4 and 0.1 M of sucrose (30). Sivakumar et al (31) described the importance of biorhizomes, rhizome specific genes/gene which over expressed in rhizomes for the biomanufacture of colchicine as root, callus and cell suspension of G. superba and various species of Colchicum yielded poor level of colchicine.…”

PIONEERING in vitro STUDIES FOR CALLUS FORMATION OF Colchicum chalcedonicum Azn.

“…Limited number of experiments were performed about Colchicum tissue culture (Hayashi et al 1988, Khan et al 2011, Daradkeh et al 2012, Wagh et al 2015. In our sterilization protocol, we used 0.25% (w/v) HgCl2 for surface sterilization, while Wagh et al (2015) used 0.15% (w/v) HgCl2 for surface sterilization of C. luteum Baker corms.…”

“…Different parts of C. chalcedonicum and C. micranthum Boiss., which are endemic for Turkey, were also investigated for cytotoxic activities for future medical approaches. Daradkeh et al (2012) managed to isolate colchicine, colchifoline, 2-demethylcolchicine, demecolcine, 4-hydroxycolchicine and N-deacetyl-Nformylcolchicine which showed high cytotoxicity. The main alkaloids of these two Colchicum species were found as colchicine and colchifoline.…”

“…Callus tissues were first induced from flowering shoots of C. autumnale L. by using MS (Murashige & Skoog 1962) containing 2,4-Dichlorophenoxyacetic acid (2,4-D), while colchicine from callus tissue was produced by MS with indole butyric acid (IBA) and kinetin (Hayashi et al 1988). Daradkeh et al (2012) used C. hierosolymitanum Feinbrun for callus production on MS supplemented with 0.45 μM 2, 4-dichlorophenoxyacetic acid under dark conditions. To induce colchicine production, callus was sub-cultured every 27 days on the same liquid media supplemented with 0.54 μM 1naphthaleneacetic acid.…”

Biorhizome: A Biosynthetic Platform for Colchicine Biomanufacturing

“…Despite considerable metabolic engineering or synthetic biotechnology efforts, the yield of bioactive alkaloid molecules are still very low in these systems because, in part, the lack of knowledge of the biosynthetic mechanism, pathways, and gene expression ( Li and Smolke, 2016 ). G. superba and colchicum species root, callus and cell cultures have been conducted in vitro , but these cultures have yielded insignificant concentrations of colchicine ( Daradkeh et al, 2012 ; Ghosh et al, 2015 ; Nikhila et al, 2017 ). Clearly, further advancement is needed to effectively overcome these barriers.…”