Cytotoxicity of 15 Cameroonian medicinal plants against drug sensitive and multi-drug resistant cancer cells

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• 作者：Victor Kuete^a ; ^b ; ^{kuetevictor@yahoo.fr" class="auth_mail" title="E-mail the corresponding author} ; Doriane E. Djeussi^b ; Armelle T. Mbaveng^b ; Maen Zeino^a ; Thomas Efferth^a ; ^{efferth@uni-mainz.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ASF ; Anthocleista Schweinfurthii Fruits ; DCF ; Dichlorofluorescein ; DMSO ; Dimethylsufoxide ; ESB ; Erythrina Sigmoidea Bark ; H2DCFH-DA ; 2&prime ; 7&prime ; -Dichlorodihydrofluorescein Diacetate ; IC50 ; Inhibitory Concentrations 50% ; JC-1 ; 5 ; 5&prime ; 6 ; 6&prime ; -Tetrachloro-1 ; 1&prime ; 3 ; 3&prime ; -Tetraethylbenzimidazolylcarbocyanine Iodide ; MDR ; Multi-Drug Resistant ; MMB ; Morus mesozygia Bark ; MMP ; Mitochondrial Membrane Potential ; NLB ; Nauclea Latifolia Bark ; NLL ; Nauclea Latifolia Leaves ; PBS ; Phosphate
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：20 June 2016
• 年：2016
• 卷：186
• 期：Complete
• 页码：196-204
• 全文大小：1187 K

文摘

Cameroonian medicinal plants are traditionally used to treat many ailments, including cancer and related diseases. Cancer is characterized as a condition with complex signs and symptoms. It has been recommended that ethnopharmacological usages such as immune and skin disorders, inflammatory, infectious, parasitic and viral diseases should be taken into account when selecting plants for anticancer screenings, since these reflect disease states bearing relevance to cancer or cancer-like symptoms.

Aim of the study

The present study aims at investigating 20 methanol extracts from 15 Cameroonian medicinal plants on a panel of human cancer cell lines, including various drug-resistant phenotypes. Possible modes of action of the of the most active plant were analyzed.

Materials and methods

Methanol extracts from different plant parts (leaves, bark, roots, fruits or whole plant) were evaluated for their cytotoxicity using resazurin reduction assay on a panel of nine sensitive and multi-drug resistant (MDR) cancer cell lines. Cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were measured by flow cytometry.

Results

Prescreening of extracts at 80 µg/mL showed that 6 extracts out of 20 inhibited more than 50% proliferation of leukemia CCRF-CEM cells; these include extracts from Anthocleista schweinfurthii fruits (ASF; 48.28%), Morus mesozygia bark (MMB; 42.76%), Nauclea latifolia bark (NLB; 38.75%), Tridesmostemon omphalocarpoides bark (TOB; 38.53%), Nauclea latifolia leaves (NLL; 35.17%) and Erythrina sigmoidea bark (ESB; 33.77%). Subsequent investigations revealed IC₅₀ values below or around 20 µg/mL for extracts from MMB, NLB, NLL and ESB towards sensitive CCRF-CEM cells and its resistant P-glycoprotein over-expressing subline CEM/ADR5000. The best extract, ESB also displayed IC₅₀ values below 20 µg/mL colon carcinoma HCT116 (p53^+/+) cells with an IC₅₀ value of 19.63 µg/mL and it resistant p53 knockout subline HCT116 (p53^−/−) with an IC₅₀ value of 16.22 µg/mL.

Conclusion

Erythrina sigmoidea, Anthocleista schweinfurthii, Morus mesozygia, Nauclea latifolia, Tridesmostemon omphalocarpoides used in African traditional medicine are good cytotoxic plants that can be exploited to develop phytomedicine to fight cancers including MDR phenotypes.