Against Lung Cancer Cells: To Be, or Not to Be, That Is the Problem

Abstract

Tobacco smoke and radioactive radon gas impose a high risk for lung cancer. The radon-derived ionizing radiation and some components of cigarette smoke induce oxidative stress by generating reactive oxygen species (ROS). Respiratory lung cells are subject to the ROS that causes DNA breaks, which subsequently bring about DNA mutagenesis and are intimately linked with carcinogenesis. The damaged cells by oxidative stress are often destroyed through the active apoptotic pathway. However, the ROS also perform critical signaling functions in stress responses, cell survival, and cell proliferation. Some molecules enhance radiation-induced tumor cell killing via the reduction in DNA repair levels. Hence the DNA repair levels may be a novel therapeutic modality in overcoming drug resistance in lung cancer. Either survival or apoptosis, which is determined by the balance between DNA damage and DNA repair levels, may lender the major problems in cancer therapy. The purpose of this paper is to take a closer look at risk factor and at therapy modulation factor in lung cancer relevant to the ROS.

Figure 1

Schematic representation of the DNA repair, cell cycle arrest, and apoptosis signaling pathways. Examples of the molecule known to act on the regulatory pathways are shown.

Figure 2

Schematic representation of decay chain of uranium series and an electron shell diagram for radon. Atomic number 86 radon (Rn) is a radioactive noble gas occurring as the decay product of uranium, thorium, or radium.

Figure 3

Schematic diagram indicating the domain structures of the ATM and Rad51 proteins. The autophosphorylation sites, HEAT (Huntington's elongation factor 3, a subunit of protein phosphatase 2A, TOR1) repeats, FAT (FRAP/ATM/TRRAP) domain, FATC (FAT C-terminal) domain in ATM, and Walker's box A and B domains (ATP binding) in Rad51 are also shown.

Figure 4

Survival or apoptosis, that is, the problem in cancer therapy. The determination either survival or apoptosis is due to the balance between DNA damage via IR or chemical agents and the DNA repair levels in cells.