Isolation Of Antimigratory Chemical Constituents From Curcuma Caesia, Curcuma Aeruginosa Rhizomes And Dioscorea Bulbifera Tubers Using Human Breast Cancer Cell Lines

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Date
2021-04
Authors
Al-Amin, Md
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Universiti Sains Malaysia
Abstract
Curcuma caesia, Curcuma aeruginosa and Dioscorea bulbifera are used traditionally for the treatment of human ailments including cancer. The present study was carried out to search for antimigratory compounds from C. caesia, C. aeruginosa rhizomes and D. bulbifera tubers using breast cancer cell lines. The chemical constituents from C. caesia and C. aeruginosa rhizomes have been isolated through fractionation. The extracts of C. caesia and C. aeruginosa rhizomes showed concentration-dependent inhibition of MCF-7 and MDA-MB-231 cells. Further study showed that hexane and chloroform fractions of C. caesia rhizomes and chloroform fraction of C. aeruginosa rhizomes are the bioactive fractions that significantly inhibit the viability of breast cancer cells. The chromatographic separation afforded germacrone (1), zerumbone (2), furanodienone (3), curzerenone (4), curcumenol (5), zederone (6), curcumenone (7) and dehydrocurdione (8) from hexane fraction and curcuminol G (9), curcuzederone (10), (1S, 10S), (4S,5S)-germacrone-1(10), 4- diepoxide (11), wenyujinin B (12), alismoxide (13), aerugidiol (14), zedoarolide B (15), zedoalactone B (16) zedoarondiol (17) and isozedoarondiol (18) from chloroform fraction of C. caesia rhizomes. The chromatographic separation afforded germacrone (1), furanodienone (3), curzerenone (4), curcumenol (5) and zederone (6) from chloroform fraction of C. aeruginosa. Cell viability assay of these isolated compounds further revealed that compounds 1-4 and 10, and compounds 1, 3 and 4 are the bioactive compounds of C. caesia and C. aeruginosa, respectively. Germacrone (1) and curcuzederone (10) showed IC50 values of 246.3 and 227.2 μM against MDAMB- 231 cells, respectively. The activity of germacrone (1) and curcuzederone (10) on the migration of MDA-MB-231 cells was also investigated and the results showed that both compounds produced a significant concentration-dependent inhibitory activity. These results indicate that germacrone (1) isolated from C. caesia and C. aeruginosa rhizomes, and curcuzederone (10) isolated from C. aeruginosa rhizomes possess antimigratory activities in breast cancer cell lines. The effect of the extract and fractions of D. bulbifera tubers on cell migration was also investigated. The extract, Fr.2 and Fr. 4, showed significant inhibition in a concentration-dependent manner on the migration of MDA-MB-231 cells. Gelatin zymography assay showed that Fr.2 and Fr.4 inhibited cell migration through the modulation of MMP-2 and MMP-9 enzymes. The chromatographic separation of Frs. 2 and 4 yielded lusianthridin (19), flavanthridin (20), 4,7-dihydroxy-2,3-dimethoxyphenanthrene (21), nudol (22) catechin (23) and diosbulbin B (24). These results suggest that the antimigratory activity of D. bulbifera tubers is possibly from compounds 19-24. In conclusion, the findings presented within this thesis collectively support the traditional uses of C. caesia, C. aeruginosa and D. bulbifera and provide an insight of the potential therapeutic use of their chemical constituents to treat breast cancer.
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Pharmacy
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