Anticancer potential of rhizome extract and a labdane diterpenoid from Curcuma mutabilis plant endemic to Western Ghats of India

Zingiberaceae plants are well known for their use in ethnomedicine. Curcuma mutabilis Škorničk., M. Sabu & Prasanthk., is an endemic Zingiberaceae species from Western Ghats of Kerala, India. Here, we report for the first time, the anticancer potential of petroleum ether extract from C. mutabili...

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Bibliographic Details
Published in:Scientific reports Vol. 11; no. 1; pp. 552 - 20
Main Authors: Soumya, T., Lakshmipriya, T., Klika, Karel D., Jayasree, P. R., Manish Kumar, P. R.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 12.01.2021
Nature Publishing Group
Nature Portfolio
Subjects:
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631/80
Acute toxicity
Apoptosis
Bioactive compounds
Calcium (intracellular)
Calcium (mitochondrial)
Cancer
Cell death
Cell survival
Chemotherapy
Curcuma
Cytotoxicity
Diterpenes
DNA fingerprinting
DNA fragmentation
Endemic plants
Endemic species
Erythrocytes
Genomics
Humanities and Social Sciences
Lymphocytes
Membrane potential
Mitochondria
multidisciplinary
Peripheral blood
Petroleum ether
Phosphatidylserine
Rhizomes
Science
Science (multidisciplinary)
Transcription
Tumor cell lines
Western blotting
Zingiberaceae
Western Ghats
India
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:Zingiberaceae plants are well known for their use in ethnomedicine. Curcuma mutabilis Škorničk., M. Sabu & Prasanthk., is an endemic Zingiberaceae species from Western Ghats of Kerala, India. Here, we report for the first time, the anticancer potential of petroleum ether extract from C. mutabilis rhizome (CMRP) and a novel labdane diterpenoid, ( E )-14, 15-epoxylabda-8(17), 12-dien-16-al (Cm epoxide) isolated from it. CMRP was found to be a mixture of potent bioactive compounds including Cm epoxide. Both the extract and the compound displayed superior antiproliferative activity against several human cancer cell lines, without any display of cytotoxicity towards normal human cells such as peripheral blood derived lymphocytes and erythrocytes. CMRP treatment resulted in phosphatidylserine externalization, increase in the levels of intracellular ROS, Ca 2+ , loss of mitochondrial membrane potential as well as fragmentation of genomic DNA. Analyses of transcript profiling and immunostained western blots of extract-treated cancer cells confirmed induction of apoptosis by both intrinsic and extrinsic pathways. The purified compound, Cm epoxide, was also found to induce apoptosis in many human cancer cell types tested. Both CMRP and the Cm epoxide were found to be pharmacologically safe in terms of acute toxicity assessment using Swiss albino mice model. Further, molecular docking interactions of Cm epoxide with selected proteins involved in cell survival and death were also indicative of its druggability. Overall, our findings reveal that the endemic C. mutabilis rhizome extract and the compound Cm epoxide isolated from it are potential candidates for development of future cancer chemotherapeutics.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-79414-8