Girish Sharma1, Rana P Singh, Daniel C Chan, Rajesh Agarwal. 1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Box C238, Denver, CO 80262, USA.
Abstract
BACKGROUND: The high systemic toxicity of chemotherapeutic agents limits their use to treat clinical lung cancer. These limitations could be minimized/overcome by using non-toxic phytochemicals, like, silibinin. MATERIALS AND METHODS: We used small cell lung carcinoma cells (SCLC) SHP-77 and non-small cell lung carcinoma cells (NSCLC) A-549, analyzing cell growth inhibition and death with Trypan blue exclusion, indices of the cell cycle progression with flow cytometry and apoptosis with propidium iodide and Hoechst 33342. RESULTS: Silibinin (25, 50 and 100 microM) treatment of SHP-77 and A-549 cells resulted in their growth inhibition and cell death. Cell cycle studies showed a small increase in G0-G1 population at all the time intervals in SHP-77 cells, however, in A-549 cells, a slight increase in G0-G1 but strong increase in S-phases was observed at lower treatment times, and a strong increase in G0-G1 population at 72 hours. Quantitative apoptotic studies showed that silibinin causes apoptotic cell death in both a dose- and a time-dependent manner with SHP-77 cells showing more apoptotic effect than A-549 cells. CONCLUSION: Silibinin significantly induces growth inhibition, a moderate cell cycle arrest and a strong apoptotic death in both small cell and non-small cell human lung carcinoma cells, which warrants further studies to assess the efficacy of this non-toxic agent in animal lung tumor models.
BACKGROUND: The high systemic toxicity of chemotherapeutic agents limits their use to treat clinical lung cancer. These limitations could be minimized/overcome by using non-toxic phytochemicals, like, silibinin. MATERIALS AND METHODS: We used small cell lung carcinoma cells (SCLC) SHP-77 and non-small cell lung carcinoma cells (NSCLC) A-549, analyzing cell growth inhibition and death with Trypan blue exclusion, indices of the cell cycle progression with flow cytometry and apoptosis with propidium iodide and Hoechst 33342. RESULTS:Silibinin (25, 50 and 100 microM) treatment of SHP-77 and A-549 cells resulted in their growth inhibition and cell death. Cell cycle studies showed a small increase in G0-G1 population at all the time intervals in SHP-77 cells, however, in A-549 cells, a slight increase in G0-G1 but strong increase in S-phases was observed at lower treatment times, and a strong increase in G0-G1 population at 72 hours. Quantitative apoptotic studies showed that silibinin causes apoptotic cell death in both a dose- and a time-dependent manner with SHP-77 cells showing more apoptotic effect than A-549 cells. CONCLUSION:Silibinin significantly induces growth inhibition, a moderate cell cycle arrest and a strong apoptotic death in both small cell and non-small cell humanlung carcinoma cells, which warrants further studies to assess the efficacy of this non-toxic agent in animal lung tumor models.
Authors: Alpna Tyagi; Rana P Singh; Kumaraguruparan Ramasamy; Komal Raina; Elizabeth F Redente; Lori D Dwyer-Nield; Richard A Radcliffe; Alvin M Malkinson; Rajesh Agarwal Journal: Cancer Prev Res (Phila) Date: 2009-01