ANTIPROLIFERATIVE EFFECT OF EXTRACTS AND FLAVONOIDS OF Juniperus Phoenicea L. GROWING IN EGYPT
Objective: To Investigate the Cytotoxic effect of the plant Juniperus phoenicea L. growing in Egypt. Main outcome measures: SRB and MTT assays are used to measure the antiproliferative activity of crude and successive extracts as well as the isolated flavonoids. Also, in vivo cytogenetic assays were carried out. Results: The antiproliferative effect of leaves crude extract of Juniperus phoenicea L. done by SRB assay showed high activity against lung carcinoma (H460), liver tumor (HEPG2) and breast carcinoma (MCF7) cell lines (IC50= 0.6, 0.9 and 4.9 µg/mL, respectively). Consecutively, among the successive extracts of leaves, the ethyl acetate fraction was the most active against (H460) (IC50=7.29 µg/mL). On the other hand, the antiproliferative effect of berries crude extract of J. phoenicea done by MTT assay showed 21% lethality at conc. 100 ppm against HEPG2. Phytochemical investigation of J. phoenicea resulted in the isolation and identification of 4 flavonoids; isoetin-7-O-β-glucoside which was isolated for the first time from berries extract, isoscutellarein, amentoflavone and agathisflavone which was isolated for the first time from leaves and berries extracts. Investigating the antiproliferative activity of the isolated flavonoids by MTT assay revealed that agathisflavone recorded high activity against HEPG2, colon carcinoma (HC112) and (H460) (IC50 =3.5, 53.1 and 59.9 µg/mL, respectively). In vivo cytogenetic assays (Micronucleus and Chromosome aberrations tests) were carried out on agathisflavone showed that no significant differences between treated and negative control groups were observed in the Micronucleus level in polychromatic erythrocytes and in chromosome aberrations in both tests, respectively, which indicates the safety of agathisflavone on normal cells. Conclusion: Juniperus phoenicea leaves exhibited more efficient antiproliferative activity than berries. Also, the biflavone; agathisflavone, isolated for the first time from leaves and berries showed the potent antiproliferative effect on cancer cell lines and is safe for normal cells of mice under the experimental conditions. Keywords: Juniperus phoenicea, flavonoids, antiproliferative activity, Micronucleus, Chromosome aberrations.