Anticancer Activities of Six Selected Natural Compounds of Some Cameroonian Medicinal Plants

BACKGROUND: Natural products are well recognized as sources of drugs in several human ailments. In the present work, we carried out a preliminary screening of six natural compounds, xanthone V(1) (1); 2-acetylfuro-1,4-naphthoquinone (2); physcion (3); bisvismiaquinone (4); vismiaquinone (5); 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone (6) against MiaPaCa-2 pancreatic and CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000. Compounds 1 and 2 were then tested in several other cancer cells and their possible mode of action were investigated. METHODOLOGY/FINDINGS: The tested compounds were previously isolated from the Cameroonian medicinal plants Vismia laurentii (1, 3, 4, 5 and 6) and Newbouldia laevis (2). The preliminary cytotoxicity results allowed the selection of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, which were then tested on a panel of cancer cell lines. The study was also extended to the analysis of cell cycle distribution, apoptosis induction, caspase 3/7 activation and the anti-angiogenic properties of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone. IC(50) values around or below 4 µg/ml were obtained on 64.29% and 78.57% of the tested cancer cell lines for xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, respectively. The most sensitive cell lines (IC(50)<1 µg/ml) were breast MCF-7 (to xanthone V(1)), cervix HeLa and Caski (to xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone), leukemia PF-382 and melanoma colo-38 (to 2-acetylfuro-1,4-naphthoquinone). The two compounds showed respectively, 65.8% and 59.6% inhibition of the growth of blood capillaries on the chorioallantoic membrane of quail eggs in the anti-angiogenic assay. Upon treatment with two fold IC(50) and after 72 h, the two compounds induced cell cycle arrest in S-phase, and also significant apoptosis in CCRF-CEM leukemia cells. Caspase 3/7 was activated by xanthone V(1). CONCLUSIONS/SIGNIFICANCE: The overall results of the present study provided evidence for the cytotoxicity of compounds xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, and bring supportive data for future investigations that will lead to their use in cancer therapy

New Azulene-Type Sesquiterpenoids from the Fruiting Bodies of Lactarius deliciosus

Abstract In the 1H NMR-guided fractionation of extracts from the edible mushroom Lactarius deliciosus, two new azulene-type sesquiterpenoids, 7-isopropenyl-4-methyl-azulene-1-carboxylic acid (1) and 15-hydroxy-3,6-dihydrolactarazulene (2), together with seven known compounds were characterized. Their structures were determined on basis of spectroscopic evidence, as well as by comparing with literature data. Amongst the known metabolites, the 13C NMR assignment of 15-hydroxy-6,7-dihydrolactarazulene (3) is reported here for the first time. Moreover, 7-acetyl-4-methylazulene-1-carbaldehyde (5) displayed a moderate antibacterial activity against Staphylococcus aureus. Graphical Abstract *Digital image of L. deliciosus. Retrieved March 17, 2017 from https://upload.wikimedia.org/wikipedia/commons/e/e3/Lactarius_deliciosus_1_(1).jpg

Cytotoxicity of compounds <b>1</b>, <b>2</b> and doxorubicin on different cancer cell lines.

<p>*EC₅₀: effective dose showing 50% inhibition of growth proliferation.</p

Cell cycle distribution with Leukemia CCRF-CEM treated with compounds 2.

<p><b>A1</b>: control after 24 h; <b>A2</b>: control after 48 h; <b>A3</b>: control after 72 h; <b>B1</b>: treated with 2×IC₅₀ after 24 h; <b>B2</b>: treated with 2×IC₅₀ after 48 h; <b>B3</b>: treated with 2×IC₅₀ after 72 h; <b>C1</b>: treated with 2×IC₅₀ after 24 h; <b>C2</b>: treated with 2×IC₅₀ after 48 h; <b>C3</b>: treated with 2×IC₅₀ after 72 h; <b>D1</b>: treated with 2×IC₅₀ after 24 h; <b>D2</b>: treated with 2×IC₅₀ after 48 h; <b>D3</b>: treated with 2×IC₅₀ after 72 h.</p

Growth percentage (%) of compounds and doxorubicin tested at 20 µg/ml on CCRF-CEM, CEM/ADR5000 and MiaPaCa-2 cell lines.

<p><b>1:</b> xanthone V₁, <b>2:</b> 2-acetylfuro-1,4-naphthoquinone; <b>3:</b> physcion; <b>4:</b> bisvismiaquinone; <b>5:</b> vismiaquinone; <b>6:</b> 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone. Data with different superscript letters are significantly different (P<0.05).</p

Cell cycle distribution with Leukemia CCRF-CEM treated with compounds 1.

<p><b>A1</b>: control after 24 h; <b>A2</b>: control after 48 h; <b>A3</b>: control after 72 h; <b>B1</b>: treated with 2×IC₅₀ after 24 h; <b>B2</b>: treated with 2×IC₅₀ after 48 h; <b>B3</b>: treated with 2×IC₅₀ after 72 h; <b>C1</b>: treated with 2×IC₅₀ after 24 h; <b>C2</b>: treated with 2×IC₅₀ after 48 h; <b>C3</b>: treated with 2×IC₅₀ after 72 h; <b>D1</b>: treated with 2×IC₅₀ after 24 h; <b>D2</b>: treated with 2×IC₅₀ after 48 h; <b>D3</b>: treated with 2×IC₅₀ after 72 h.</p

Enzymatic activity of caspase 3/7 after 6 h treatment of CCRF-CEM cells with compounds 1.

<p>The activity of caspase 3/7 is expressed as percentage % relative to untreated cells. Compound <b>2</b> did not show any induction of caspase 3/7 activity (data not shown). Values are mean ± SD of three duplicated experiments.</p

Chemical structures of the studied compounds.

<p><b>1:</b> xanthone V₁, <b>2:</b> 2-acetylfuro-1,4-naphthoquinone; <b>3:</b> physcion; <b>4:</b> bisvismiaquinone; <b>5:</b> vismiaquinone; <b>6:</b> 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone.</p