Molecular Basis and Potential Molecular Mechanisms of Action in Natural Products as Therapeutic Agents Towards Multiple Myeloma

Abstract

Multiple myeloma (MM) is a bone marrow-based neoplasm of clonal plasma cells resulting in substantial mortality and morbidity. It is classified as a mature B-cell neoplasm in which clonal plasma cell proliferation results in anaemia, hypercalcaemia and organ/tissue damage such as kidneys and skeletal system. The response rates of myeloma improved significantly following the introduction of novel therapies such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), monoclonal antibodies (MoAbs), hematopoietic stem cell transplant and cellular therapies such as chimeric antigen receptor (CAR) T-cells. However, MM remains incurable. In addition, adverse effects, exorbitant costs, and problems with accessibility to drugs and therapeutic modalities prevent many patients from reaping the potential benefits of these novel therapies. Therefore, it is essential to investigate new therapeutic targets and agents. Many cell signalling pathways are described in MM. Some facilitate the evasion of apoptosis and long periods of cell survival. Natural products contain a variety of secondary metabolites targeting these signalling pathways responsible for anti-MM activities such as apoptosis, cell cycle arrest, anti-angiogenesis, and miRNA modulation. The role of natural compounds as therapeutic agents in the treatment of multiple myeloma has drawn a considerable interest in research in recent past. This review attempts to collate available information on natural products from terrestrial plants, animals, and macrofungi, and their potential molecular mechanisms in MM.