Natural bio-drugs as matrix metalloproteinase inhibitors: new perspectives on the horizon?

The matrix metalloproteinases (MMPs), belonging to the family of proteolytic enzymes, are well-known for their ability to degrade the extracellular matrix, and are involved in many aspects of both physiological cellular processes and pathological situations, such as tumor growth, invasion and metastasis. MMPs have been considered prognostic factors in various types of cancer as well as promising targets for cancer therapy. Although preclinical studies of a number of different synthetic MMP inhibitors have been identified as cytostatic and anti-angiogenic agents and have begun clinical testing, the past years have produced a consistent number of disappointments and limited successes. In view of their specific implication in malignant tissues, several natural compounds were utilized, and the results were so satisfactory as to encourage several clinical trials in order to improve efficacy and to reduce the side effect profile. The natural protection against cancer has been receiving a great deal of attention, and the critical examination of previous studies shed light on new information about the source and function of MMPs, focusing the attention on the identification of MMP targets in tumors. This review discusses the current knowledge and research in the field of natural MMP inhibitor as innovative therapeutic intervention in cancer.