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Cytotoxicity of selected Cameroonian medicinal plants and Nauclea pobeguinii towards multi-factorial drug-resistant cancer cells.

Kuete V, Sandjo LP, Mbaveng AT, Seukep JA, Ngadjui BT, Efferth T - BMC Complement Altern Med (2015)

Bottom Line: The lowest IC50 value was obtained with the bark extract of N. pobeguinii against HCT116 (p53 (-/-) ) colon cancer cells (8.70 μg/mL).Compounds 4 and 6 displayed selective activity on leukemia and carcinoma cells, whilst 1-3 were not active.Collateral sensitivity was observed in CEM/ADR5000 leukemia cells, MDA-MB-231-BCRP breast adenocarcinoma cells (0.53-fold), HCT116 (p53 (+/+) ) cells, human U87MG.ΔEGFR glioblastome multiforme cells to the methanolic bark extract of N. pobeguinii, as well as in MDA-MB-231-BCRP cells and HCT116 (p53 (+/+) ) cells and U87MG.ΔEGFR cells (0.86-fold) to compound 5.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128, Mainz, Germany. kuetevictor@yahoo.fr.

ABSTRACT

Background: Malignacies are still a major public concern worldwide and despite the intensive search for new chemotherapeutic agents, treatment still remains a challenging issue. This work was designed to assess the cytotoxicity of six selected Cameroonian medicinal plants, including Nauclea pobeguinii and its constituents 3-acetoxy-11-oxo-urs-12-ene (1), p-coumaric acid (2), citric acid trimethyl ester (3), resveratrol (4), resveratrol β- D -glucopyranoside (5) and strictosamide (6), against 8 drug-sensitive and multidrug-resistant (MDR) cancer cell lines.

Methods: The resazurin reduction assay was used to evaluate the cytotoxicity of the crude extracts and compounds, whilst column chromatography was used to isolate the constituents of Nauclea pobeguinii. Structural characterization of isolated compounds was performed using nuclear magnetic resonance (NMR) spectroscopic data.

Results: Preliminary experiments on leukemia CCRF-CEM cells at 40 μg/mL showed that the leaves and bark extracts from Tragia benthamii, Canarium schweinfurthii, Myrianthus arboreus, Dischistocalyx grandifolius and Fagara macrophylla induced more than 50 % growth of this cell line contrary to the leaves and bark extracts of N. pobeguinii. IC50 values below or around 30 μg/mL were obtained with leaves and bark extracts of N. pobeguinii towards two and five, respectively, of the 8 tested cancer cell lines. The lowest IC50 value was obtained with the bark extract of N. pobeguinii against HCT116 (p53 (-/-) ) colon cancer cells (8.70 μg/mL). Compounds 4 and 6 displayed selective activity on leukemia and carcinoma cells, whilst 1-3 were not active. IC50 values below 100 μM were recorded with compound 5 on all 9 tested cancer cell lines as well as with 4 against 7 out of 8 and 6 against 2 out of 8 cell lines. Collateral sensitivity was observed in CEM/ADR5000 leukemia cells, MDA-MB-231-BCRP breast adenocarcinoma cells (0.53-fold), HCT116 (p53 (+/+) ) cells, human U87MG.ΔEGFR glioblastome multiforme cells to the methanolic bark extract of N. pobeguinii, as well as in MDA-MB-231-BCRP cells and HCT116 (p53 (+/+) ) cells and U87MG.ΔEGFR cells (0.86-fold) to compound 5.

Conclusions: The results of this study demonstrate the cytotoxicity of six Cameroonian medicinal plants, Canarium schweinfurthii, Dischistocalyx grandifolius, Tragia benthamii, Fagara macrophylla, Myrianthus arboreus and Nauclea pobeguinii. We also demonstrated the antiproliferative potential of Nauclea pobeguinii against drug-resistant cancer cell lines. Resveratrol and its glucoside are the major cytotoxic constituents in the bark of Nauclea pobeguinii.

No MeSH data available.


Related in: MedlinePlus

Growth percentage (%) of CCRF-CEM leukemia cells treated with plant extracts and doxorubicin. Samples were tested at a single concentration of 40 mg/mL for crude extracts and of 10 μM for doxorubicin
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Fig2: Growth percentage (%) of CCRF-CEM leukemia cells treated with plant extracts and doxorubicin. Samples were tested at a single concentration of 40 mg/mL for crude extracts and of 10 μM for doxorubicin

Mentions: A preliminary cytotoxicity study was first carried out on leukemia CCRF-CEM cells with crude extracts at a single concentration of 40 μg/mL for crude extracts. Doxorubicin (10 μM) served as positive control. According to the National Cancer Institute (USA), 30 μg/mL is the upper IC50 limit considered promising for purification of a crude extract [33]. We tested a slightly higher concentration (of 40 μg/mL) in our preliminary assay. The results depicted in Fig. 2 show that more than 50 % growth was obtained if CCRF-CEM cells were treated with the methanol extracts from Tragia benthamii (63.7 %), Canarium schweinfurthii (59.96 %), Myrianthus arboreus (57.8 %), Dischistocalyx grandifolius (56.8 %) and Fagara macrophylla leaves (52.0 %). Only the crude extracts from the leaves (36.6 %) and bark (33.0 %) of Nauclea pobeguinii as well as doxorubicin (13.6 %) were able to induce more than 50 % inhibition of CCRF-CEM leukemia cell growth (Fig. 2). The IC50 values of extracts (bark and leaves) from Nauclea pobeguinii were further determined on eight cancer cell lines and values below 30 μg/mL were obtained both extracts towards two out of eight and five out of eight cell lines, respectively (Table 2). The lowest IC50 value of 8.70 μg/mL was obtained with the bark extract against HCT116 (p53−/−) cells. Consequently, this extract was subjected to purification from which six compounds (1–6) were obtained. Compounds 4 and 6 displayed selective activities on the studied cancer cell lines. IC50 values below 100 μM were recorded with compound 5 on all eight tested cancer cell lines. IC50 values below 175.36 μM and 80.29 μM (for 4 and 6 respectively) were also obtained against seven out of eight cell lines for 4 and two out of eight cell lines for 6. The IC50 values ranged from 25.08 μM (towards CCRF-CEM cells) to 97.64 (towards MDA-MB231 cells) for compound 5 and from 0.20 μM (against CCRF-CEM cells) and 195.12 μM (against CEM/ADR5000 cells) for doxorubicin. No IC50 values were obtainable, if compound 1 was tested at up to 82.92 μM. The same is true for compounds 2 (>243.90 μM) and 3 (>170.94 μM). The best compounds (4 and 5) were less toxic towards AML12 normal hepatocytes than against cancer cells. The IC50 threshold values of 20 μg/mL for crude extracts as well as 4 μg/mL or 10 μM for compounds [34, 35] after 48 and 72 h incubation have been set by the United States National Cancer Institute (USNCI) to identify good cytotoxic phytochemicals. None of the tested compounds displayed IC50 values below 10 μM. However, the bark extract of Nauclea pobeguinii (IC50 value below 20 μg/mL on four out of eight tested cancer cell lines) could be considered as a promising candidate to fight cancers. The best isolated compounds (4–6) displayed rather moderate activities, suggesting possible synergistic effects of constituents in the crude extract.Fig. 2


Cytotoxicity of selected Cameroonian medicinal plants and Nauclea pobeguinii towards multi-factorial drug-resistant cancer cells.

Kuete V, Sandjo LP, Mbaveng AT, Seukep JA, Ngadjui BT, Efferth T - BMC Complement Altern Med (2015)

Growth percentage (%) of CCRF-CEM leukemia cells treated with plant extracts and doxorubicin. Samples were tested at a single concentration of 40 mg/mL for crude extracts and of 10 μM for doxorubicin
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4559964&req=5

Fig2: Growth percentage (%) of CCRF-CEM leukemia cells treated with plant extracts and doxorubicin. Samples were tested at a single concentration of 40 mg/mL for crude extracts and of 10 μM for doxorubicin
Mentions: A preliminary cytotoxicity study was first carried out on leukemia CCRF-CEM cells with crude extracts at a single concentration of 40 μg/mL for crude extracts. Doxorubicin (10 μM) served as positive control. According to the National Cancer Institute (USA), 30 μg/mL is the upper IC50 limit considered promising for purification of a crude extract [33]. We tested a slightly higher concentration (of 40 μg/mL) in our preliminary assay. The results depicted in Fig. 2 show that more than 50 % growth was obtained if CCRF-CEM cells were treated with the methanol extracts from Tragia benthamii (63.7 %), Canarium schweinfurthii (59.96 %), Myrianthus arboreus (57.8 %), Dischistocalyx grandifolius (56.8 %) and Fagara macrophylla leaves (52.0 %). Only the crude extracts from the leaves (36.6 %) and bark (33.0 %) of Nauclea pobeguinii as well as doxorubicin (13.6 %) were able to induce more than 50 % inhibition of CCRF-CEM leukemia cell growth (Fig. 2). The IC50 values of extracts (bark and leaves) from Nauclea pobeguinii were further determined on eight cancer cell lines and values below 30 μg/mL were obtained both extracts towards two out of eight and five out of eight cell lines, respectively (Table 2). The lowest IC50 value of 8.70 μg/mL was obtained with the bark extract against HCT116 (p53−/−) cells. Consequently, this extract was subjected to purification from which six compounds (1–6) were obtained. Compounds 4 and 6 displayed selective activities on the studied cancer cell lines. IC50 values below 100 μM were recorded with compound 5 on all eight tested cancer cell lines. IC50 values below 175.36 μM and 80.29 μM (for 4 and 6 respectively) were also obtained against seven out of eight cell lines for 4 and two out of eight cell lines for 6. The IC50 values ranged from 25.08 μM (towards CCRF-CEM cells) to 97.64 (towards MDA-MB231 cells) for compound 5 and from 0.20 μM (against CCRF-CEM cells) and 195.12 μM (against CEM/ADR5000 cells) for doxorubicin. No IC50 values were obtainable, if compound 1 was tested at up to 82.92 μM. The same is true for compounds 2 (>243.90 μM) and 3 (>170.94 μM). The best compounds (4 and 5) were less toxic towards AML12 normal hepatocytes than against cancer cells. The IC50 threshold values of 20 μg/mL for crude extracts as well as 4 μg/mL or 10 μM for compounds [34, 35] after 48 and 72 h incubation have been set by the United States National Cancer Institute (USNCI) to identify good cytotoxic phytochemicals. None of the tested compounds displayed IC50 values below 10 μM. However, the bark extract of Nauclea pobeguinii (IC50 value below 20 μg/mL on four out of eight tested cancer cell lines) could be considered as a promising candidate to fight cancers. The best isolated compounds (4–6) displayed rather moderate activities, suggesting possible synergistic effects of constituents in the crude extract.Fig. 2

Bottom Line: The lowest IC50 value was obtained with the bark extract of N. pobeguinii against HCT116 (p53 (-/-) ) colon cancer cells (8.70 μg/mL).Compounds 4 and 6 displayed selective activity on leukemia and carcinoma cells, whilst 1-3 were not active.Collateral sensitivity was observed in CEM/ADR5000 leukemia cells, MDA-MB-231-BCRP breast adenocarcinoma cells (0.53-fold), HCT116 (p53 (+/+) ) cells, human U87MG.ΔEGFR glioblastome multiforme cells to the methanolic bark extract of N. pobeguinii, as well as in MDA-MB-231-BCRP cells and HCT116 (p53 (+/+) ) cells and U87MG.ΔEGFR cells (0.86-fold) to compound 5.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128, Mainz, Germany. kuetevictor@yahoo.fr.

ABSTRACT

Background: Malignacies are still a major public concern worldwide and despite the intensive search for new chemotherapeutic agents, treatment still remains a challenging issue. This work was designed to assess the cytotoxicity of six selected Cameroonian medicinal plants, including Nauclea pobeguinii and its constituents 3-acetoxy-11-oxo-urs-12-ene (1), p-coumaric acid (2), citric acid trimethyl ester (3), resveratrol (4), resveratrol β- D -glucopyranoside (5) and strictosamide (6), against 8 drug-sensitive and multidrug-resistant (MDR) cancer cell lines.

Methods: The resazurin reduction assay was used to evaluate the cytotoxicity of the crude extracts and compounds, whilst column chromatography was used to isolate the constituents of Nauclea pobeguinii. Structural characterization of isolated compounds was performed using nuclear magnetic resonance (NMR) spectroscopic data.

Results: Preliminary experiments on leukemia CCRF-CEM cells at 40 μg/mL showed that the leaves and bark extracts from Tragia benthamii, Canarium schweinfurthii, Myrianthus arboreus, Dischistocalyx grandifolius and Fagara macrophylla induced more than 50 % growth of this cell line contrary to the leaves and bark extracts of N. pobeguinii. IC50 values below or around 30 μg/mL were obtained with leaves and bark extracts of N. pobeguinii towards two and five, respectively, of the 8 tested cancer cell lines. The lowest IC50 value was obtained with the bark extract of N. pobeguinii against HCT116 (p53 (-/-) ) colon cancer cells (8.70 μg/mL). Compounds 4 and 6 displayed selective activity on leukemia and carcinoma cells, whilst 1-3 were not active. IC50 values below 100 μM were recorded with compound 5 on all 9 tested cancer cell lines as well as with 4 against 7 out of 8 and 6 against 2 out of 8 cell lines. Collateral sensitivity was observed in CEM/ADR5000 leukemia cells, MDA-MB-231-BCRP breast adenocarcinoma cells (0.53-fold), HCT116 (p53 (+/+) ) cells, human U87MG.ΔEGFR glioblastome multiforme cells to the methanolic bark extract of N. pobeguinii, as well as in MDA-MB-231-BCRP cells and HCT116 (p53 (+/+) ) cells and U87MG.ΔEGFR cells (0.86-fold) to compound 5.

Conclusions: The results of this study demonstrate the cytotoxicity of six Cameroonian medicinal plants, Canarium schweinfurthii, Dischistocalyx grandifolius, Tragia benthamii, Fagara macrophylla, Myrianthus arboreus and Nauclea pobeguinii. We also demonstrated the antiproliferative potential of Nauclea pobeguinii against drug-resistant cancer cell lines. Resveratrol and its glucoside are the major cytotoxic constituents in the bark of Nauclea pobeguinii.

No MeSH data available.


Related in: MedlinePlus