Review Article on Molecular Basis of Zinc and Copper Interactions in Cancer Physiology.

Abstract

Various clinical manifestations associated with measurable abnormalities of Zn and Cu in serum and tissue were determined in Cancer-Patients (CP), and therefore, these two metals are drawing more and more attention presently than ever before. Cancer is a disease of uncontrolled-abnormal-cell-division with invasion-potential which was exhibited to occur due to dys-regulation/dys-homeostasis of fundamental-biological-pathways (FBP) including antioxidant-enzyme-defense-system, anti-inflammatory and immune-systems, and DNA-damage-repair-system in the human-body resulting in generation of chronic-oxidative-stress induced DNA-damage and gene-mutations, inflammation and compromised immune-system, tumor-induced increased angiogenesis, and inhibition of apoptosis processes. Zn and Cu were recognized to be the most crucial components of FBP and imbalance in Zn/Cu ratios in CP asserted to generate chronic toxicity in human body through various mechanisms including increased chronic oxidative stress linked compromised DNA integrity and gene mutations due to malfunctioning of DNA damage repair enzymes; increased angiogenesis process due to Zn- and Cu-binding proteins metallothionein and ceruloplasmin-induced enhanced expression of tumor growth factors; and elevation in inflammatory response which was further shown to down/upregulate gene expression of multiple Zn transporter proteins leading to dys-homeostasis of intracellular Zn concentrations, and it was determined to disturb the equilibrium between cell growth and division, proliferation, differentiation, and apoptosis processes which lead to cancer progression. Moreover, Zn was reported to affect matrix metalloproteinase activity and influence immune system cells to respond differently to different cytokines and enhance immune-suppressive effects accelerating the angiogenesis, invasion, and metastasis potential in cancer. Further, the most significant use of serum Cu/Zn ratio was recommended in clinical diagnosis, prognosis, tumor stage, patient survival, and cancer follow-up studies which need further investigations to elucidate and explore their roles in cancer physiology for clinical perspective.