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Anti-cancer labdane diterpenoids from adventitious roots of Andrographis paniculata: augmentation of production prospect endowed with pathway gene expression

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Abstract

Andrographolide (AD) is the time-honoured pharmacologically active constituent of the traditionally renowned medicinal plant—Andrographis paniculata. Advancements in the target-oriented drug discovery process have further unravelled the immense therapeutic credibility of another unique molecule—neoandrographolide (NAD). The escalated market demand of these anti-cancer diterpenes is increasingly facing unrelenting hurdles of demand and supply disparity, attributable to their limited yield. Callus and adventitious root cultures were generated to explore their biosynthetic potentials which first time revealed NAD production along with AD. Optimization of the types and concentrations of auxins along with media form and cultivation time led to the successful tuning towards establishing adventitious roots as a superior production alternative for both AD/NAD. Supplementation of IBA to the NAA + Kn-containing MS medium boosted the overall growth and AD/NAD synthesis in the adventitious roots. Compared to control leaves, the adventitious root exhibited about 2.61- and 8.8-fold higher contents of AD and NAD, respectively. The qRT-PCR involving nine key pathway genes was studied, which revealed upregulation of GGPS1 and HMGR1/2 genes and downregulation of DXS1/2 and HDR1/2 genes in the adventitious root as compared to that in the control leaves. Such observations highlight that in vitro cultures can serve as efficient production alternatives for AD/NAD as the cytosolic genes (HMGR1/2 of MVA pathway) are competent enough to take over from the plastidial genes (DXS1/2 and HDR1/2 of MEP pathway), provided the accredited first branch-point regulatory gene (GGPS) expression and the culture requirements are optimally fulfilled.

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Acknowledgements

The authors wish to express their sincere thanks to the Director, CSIR-CIMAP, for providing the facilities to carry out this research. SB is thankful to the National Academy of Sciences (NASI, Allahabad, India), for honouring her as a Platinum Jubilee Senior Scientist and providing the financial support to continue the research. SS is also thankful to NASI, Allahabad, India, and PP to the Department of Science and Technology (DST, New Delhi, India), for financial support in the form of fellowships. This work is carried out under a NASI project (GAP-365).

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  1. Sailendra Singh and Pallavi Pandey contributed equally to this work.

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  1. Department of Plant Biotechnology, Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, 226015, India

    Sailendra Singh, Pallavi Pandey, Sumit Ghosh & Suchitra Banerjee

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  1. Sailendra Singh
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Correspondence to Suchitra Banerjee.

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Singh, S., Pandey, P., Ghosh, S. et al. Anti-cancer labdane diterpenoids from adventitious roots of Andrographis paniculata: augmentation of production prospect endowed with pathway gene expression. Protoplasma 255, 1387–1400 (2018). https://doi.org/10.1007/s00709-018-1211-7

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