Pharmacogenomics of Cameroonian traditional herbal medicine for cancer therapy.

BACKGROUND

A socio-economic burden associated with cancers is reported in Africa. Ethnopharmacological usages such as immune and skin disorders, inflammatory, and others chould be considered when selecting plants used to treat cancer, since these reflect disease states bearing relevance to cancer or a cancer symptoms.

METHODS

Documented compounds of Cameroonian medicinal plants were used as keywords in the National Cancer Institute (NCI) database to establish a library of cytotoxic compounds. Cellular and pharmacogenomic profiling was then performed for the 10 most cytotoxic natural products. By COMPARE and hierarchical cluster analyses, candidate genes were identified whose mRNA expression significantly predicted sensitivity or resistance of cell lines to the two most cytotoxic compounds.

RESULTS

Up to 974 compounds isolated from 148 medicinal plants were used as keywords in the NCI database to establish a library of 27 cytotoxic compounds. Two of the 10 most cytotoxic compounds, plumericin from Plumeria rubra and plumbagin from Diospyros crassiflora and Diospyros canaliculata, were analyzed in more detail. The IC(50) values for plumericin and plumbagin of 60 NCI cell lines were associated with the microarray-based transcriptome-wide mRNA expression. Genes products identified for plumericin activity are mainly involved in enzymatic activity, transcriptional processes or are structural constituents of ribosomes. Products identified for plumbagin activity are involved in several processes, but they are mostly the strucrural constituents of ribosomes or involved in enzymatic activity.

CONCLUSIONS

The most significant progress of the present investigation, the first of its kind ever reported for investigated natural product in Sub-Saharan Africa, was the connection between traditionally used medicinal plants and the mechanistic analysis, such as pharmacogenomics.