Multiple myeloma (MM) is a hematological malignancy and arises from the proliferation of plasma cells in the bone marrow. It is the second common blood cancer after lymphoma, and Australia has a very high incidence of MM. Despite the availability of autologous stem cell transplantation and the development of many novel drugs, which have resulted in increasing overall survival, MM is still an incurable disease due to drug resistance or refractory disease. Thus, new drugs are required to overcome these problems.
Many plants are regarded as sources of anticancer drugs with limited or no side effects. An Australia plant called Terminalia ferdinandiana (Kakadu plum) has attracted a lot of attention due to its very high antioxidant content. The extracts of Kakadu plum have been investigated previously, and the fruit extract has demonstrated antiproliferative activities in different types of cancer cells, with low toxicity to non-cancerous cells. Therefore, Kakadu plum extracts have potential as a source of anticancer agents to combat MM.
This project assesses the cytotoxicity and antiproliferative activities of Kakadu plum extracts in MM derived cell lines, with the cellular antioxidant systems as probable therapeutic targets also examined. The upregulation of the thioredoxin antioxidant system has been reported in MM cells and it is also related to drug resistance. We have found, using MTT assays, that the leaf extracts of Kakadu plum significantly suppressed MM cell growth and had cytotoxic effects on MM cells compared to normal peripheral blood mononuclear cells. We are now assessing if the leaf extracts induce apoptosis through affecting the thioredoxin regulated NF-κB signalling pathway, which is upregulated in MM cells.