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Anticancer potential of rhizome extract and a labdane diterpenoid from Curcuma mutabilis plant endemic to Western Ghats of India.
- Source :
-
Scientific reports [Sci Rep] 2021 Jan 12; Vol. 11 (1), pp. 552. Date of Electronic Publication: 2021 Jan 12. - Publication Year :
- 2021
-
Abstract
- 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 <superscript>2+</superscript> , 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.
- Subjects :
- Animals
Apoptosis drug effects
Calcium metabolism
Cell Line, Tumor
Cell Proliferation drug effects
DNA Fragmentation drug effects
Dose-Response Relationship, Drug
Epoxy Compounds isolation & purification
Humans
India
Membrane Potential, Mitochondrial drug effects
Mice
Phosphatidylserines metabolism
Plant Extracts isolation & purification
Reactive Oxygen Species metabolism
Antineoplastic Agents, Phytogenic
Curcuma chemistry
Diterpenes isolation & purification
Diterpenes pharmacology
Epoxy Compounds pharmacology
Neoplasms pathology
Plant Extracts chemistry
Plant Roots chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33436696
- Full Text :
- https://doi.org/10.1038/s41598-020-79414-8