Unique Phenanthrenes from Juncus ensifolius and Their Antiproliferative and Synergistic Effects with the Conventional Anticancer Agent Doxorubicin against Human Cancer Cell Lines

Abstract

Phenanthrenes are the main special metabolites of Juncaceae species from phytochemical, pharmacological, and chemotaxonomical points of view. The present study focused on the isolation, structure determination, and pharmacological investigation of phenanthrenes from Juncus ensifolius. Nineteen compounds, including 17 phenanthrenes, were identified from the methanol extract of the plant. Thirteen compounds, namely, ensifolins A–M (1–13), were obtained for the first time from natural sources. Four phenanthrenes [2-hydroxy-1,7-dimethyl-5-vinyl-9,10-dihydrophenanthrene (14), juncuenin B (15), juncatrin B (16), and sylvaticin A (17)], 4-hydroxybenzaldehyde (18) and luteolin (19) were isolated for the first time from J. ensifolius. Ensifolins A (1) and B (2) are structurally unique phenanthrenes, considering that they are flavonoid- (1) or benzaldehyde-adducts (2). The antiproliferative activity of all isolated compounds against HeLa, COLO 205, and COLO 320 cancer cells and a non-tumor (MRC-5) cell line was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay. The luteolin-substituted phenanthrene ensifolin A (1) proved to be the most active against all three cancer cell lines (IC50 values 3.9–12.7 μM) and showed good selectivity (SI = 4.95) in the case of COLO 205. The best selectivity was recorded for ensifolins D (4, SI > 5.15, HeLa), H (8, SI > 8.13, HeLa), and 17 (SI > 9.43, HeLa). The synergistic activity of the compounds with doxorubicin was also tested on HeLa cells, and ensifolins E (5) and H (8) exhibited very strong synergism (CI < 0.1). In conclusion, these phenanthrenes are worthy of further investigation.

1,5,6-Trimethoxy-2,7-dihydroxyphenanthrene from Dendrobium officinale Exhibited Antitumor Activities for HeLa Cells

“…Ching [42]. These reports are partially consistent with and supporting of our results, namely that compound structures, even with minor differences, would have significant activities towards the same cell lines.…”

Polyoxypregnane Ester Derivatives and Lignans from Euphorbia gossypina var. coccinea Pax.

“…The antiproliferative assay of the isolated compounds ( 1 – 3 , 5 – 12 ) against the human cervix carcinoma (HeLa) cell line was performed by MTT, using cisplatin and doxorubicin as positive controls. This assay was carried out as previously described [ 30 , 31 ].…”