Effects of Kigelia africana, Ximenia caffra and Mimusops zeyheri seed oils on hormone-independent (MDA-MB-231) and hormone-dependent (MCF-7) breast cancer cell lines

Abstract

Breast cancer is the most prevalent type of cancer among women worldwide. The survival rate of breast cancer patients in developing countries is lower than that of their counterparts in firstworld countries, since most do not have access to conventional medicine and treatment. Consequently, the health care of these women is heavily influenced by ethnomedicine.

In sub-Saharan Africa, traditional healers use parts of Kigelia africana (K. africana), Ximenia caffra (X. caffra) and Mimusops zeyheri (M. zeyheri) trees to treat various maladies. The seed oils of K. africana, X. caffra and M. zeyheri were shown to inhibit proliferation of human colon adenocarcinoma (Caco-2) and human embryonic kidney (HEK-293) cells in vitro. Consequently the effects of these seed oils on hormone-independent MDA-MB-231 and hormone-dependent MCF-7 breast cancer cells in vitro were investigated.

The seed oils' potential toxicities were tested using the lactate dehydrogenase cytotoxicity and neutral red cell viability assays. The possible mechanism(s) by which these seed oils induced cytotoxic/anti-proliferative effects on MDA-MB-231 and MCF-7 cells were subsequently investigated using flow cytometry and enzyme-linked immunoassays. The ability of the seed oils to reduce the thrombogenic ability of breast cancer cells was also studied using flow cytometry.

Analysis of the seed oils showed that K. africana seed oil had the highest concentration of αlinolenic acid (an essential omega-3 fatty acid) followed by X. caffra and lastly M. zeyheri. M. zeyheri had the highest concentration of linoleic acid (an essential omega-6 fatty acid) followed by K. africana and X. caffra. Our results point to the effects of K. africana, X. caffra and M. zeyheri seed oils being more dependent on the fatty acid composition, the duration of exposure, as well as phenotype of the breast tumors. K. africana and X. caffra seed oils induced the greatest cytotoxic effects on MDA-MB-231 cells, while X. caffra and M. zeyheri seed oils induced a growth inhibitory effect on MCF-7 cells. Analysis by flow cytometry suggested an apoptotic mediated cell death, however low levels of caspase-6 indicated the engagement of another pathway. K. africana-treated cells showed a significant reduction in the expression of LC3A in MDA-MB-231 cells suggesting that this seed oil may inhibit autophagic activity. K. africana, X. caffra and M. zeyheri seed oils decreased the thrombogenic ability of hormoneindependent MDA-MB-231 breast cancer cells. These findings corroborate previous reports of plant seed oil's beneficial effects and supports the notion that plants can be considered for the management of diseases such as breast cancer. However further investigations are required into the mechanisms by which these seed oils exert their effects.