Silibinin induces growth inhibition and apoptotic cell death in human lung carcinoma cells.
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.


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.


CONCLUSIONS
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.
Sharma
Girish
G
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Box C238, Denver, CO 80262, USA.
Singh
Rana P
RP
Chan
Daniel C
DC
Agarwal
Rajesh
R
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D006131:Growth Inhibitors; D012838:Silymarin; D000077385:Silybin