Abstract
Objectives: The chemotherapeutic potential of Gagamgilgyung-tang for the treatment of human lung cancer, the antitumorigenic effects of Gagamgilgyung-tang on the proliferation and apoptosis of human lung cancer cell line A427 were investigated using molecular biological approaches, Methods: To determine Gagamgilgyung-tang concentrations which do not evoke cytotoxic damage to the cell line, cell viability was examined by MTT assay. To prove Gagamgilgyung-tang's antitumorigenic potential to human lung cancer, [3H]thymidine incorporation assay, trypan blue exclusion and Cpp32 protease activity assays and quantitative RT-PCR analysis were examined. Results: While A427 cells treated with $0.1-2.0{\mu\textrm{g}}/ml$ of Gagamgilgyung-tang showed no recognizable effect, marked reductions of cell viability were detected at concentrations over $5.0{\;}\mu\textrm{g}/ml$. DNA replication of A427 cells was inhibited by Gagamgilgyung-tang in a dose-dependent manner and Gagamgilgyung-tang induced the G1 cell cycle arrest through inhibition of DNA replication. Gagamgilgyung-tang triggered apoptotic cell death of A427 and enhanced the apoptotic sensitivity of the cells that were injured by a DNA damage-inducing chemotherapeutic drug etoposide. Gagamgilgyung-tang induces expression of growth-inhibiting genes such as p53 and p21/Wafl whereas it inhibited expression of growth-promoting genes such as c-Myc and Cyclin D1. Expression of a representative apoptosis-inducing gene Bax was also found to be induced by Gagamgilgyung-tang while apoptosis-suppressing Bcl-2 expression was not changed. Conclusions: Gagamgilgyung-tang could suppress the abnormal growth of tumor cells by suppressing the survival of genetically altered cells via induction of apoptosis. This study suggests that Gagamgilgyung-tang might have an antitumorigenic potential to human lung cancer cells, which might be associated with its growth-inhibiting and apoptosis-inducing properties.
