Matrix metalloproteinase enzymes and their naturally derived inhibitors: novel targets in photocarcinoma therapy

Ageing Res Rev. 2014 Jan:13:65-74. doi: 10.1016/j.arr.2013.12.001. Epub 2013 Dec 16.

Abstract

The continuous exposure of skin to ultraviolet radiations generates reactive oxygen species leading to photoaging in which degradation of dermal collagen and degeneration of elastic fibers occurs. Matrix metalloproteinase [MMP] enzymes are the proteolytic enzymes which have significant potentiality of cleaving extracellular matrix [ECM] against Ultraviolet [UV] radiation. The important MMPs are MMP1, MMP2 and MMP7 which promote skin cancer when irradiated by UV rays. In lieu of this, the investigation of MMPs and their inhibitors are constantly being studied for successive results. Recent researches have focused on some traditionally used bioactive moieties as natural matrix metalloproteinases inhibitors (MMPIs) and emphasized on the need of more extensive and specific studies on MMPIs, so that a good combination of natural or synthetic MMPIs with the conventional drugs can be evolved for cancer chemotherapy. In this review, we discuss the current view on the feasibility of MMPs as targets for therapeutic intervention in cancer. This review also summarizes the role of small molecular weight natural MMPIs and a clinical update of those natural MMPIs that are under clinical trial stage.

Keywords: Extracellular matrix; Matrix metalloproteinase; Mitogen activated protein kinase; Non melanoma skin cancer; Ultraviolet radiations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Drug Design
  • Humans
  • Matrix Metalloproteinase Inhibitors / therapeutic use*
  • Matrix Metalloproteinases / metabolism*
  • Molecular Targeted Therapy
  • Neoplasms, Radiation-Induced / drug therapy*
  • Neoplasms, Radiation-Induced / enzymology
  • Neoplasms, Radiation-Induced / pathology
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / pathology
  • Sunlight / adverse effects*
  • Ultraviolet Rays / adverse effects*

Substances

  • Antineoplastic Agents
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases