Cell growth inhibition and down-regulation of survivin by silibinin in a laryngeal squamous cell carcinoma cell line.
OBJECTIVE
Abnormalities in the regulation of apoptotic cell death have been shown to have an important effect on the pathogenesis and progression of cancer. Survivin, which is identified in most cancers and has recently been identified as an inhibitor of apoptosis, is a potential therapeutic target for cancer management. We investigated cell growth, apoptosis, and expression of survivin in laryngeal squamous cell carcinoma cell lines after treatment with the bioactive compound silibinin.


METHODS
Cultured human laryngeal squamous cell carcinoma SNU-46 cells were treated with different concentrations of silibinin, and the degree of cell growth and apoptosis was analyzed. Additionally, survivin protein and messenger RNA were analyzed by Western immunoblotting and reverse transcription-polymerase chain reaction.


RESULTS
Silibinin inhibited the growth of SNU-46 cells in a both dose- and time-dependent manner (p < 0.01). Upon fluorescence-activated cell sorter analysis, silibinin (200 micromol/L) treatment increased the proportion of apoptotic cells from 7% to 40%. At high concentrations (more than 150 micromol/L), silibinin greatly reduced messenger RNA and protein expression of survivin.


CONCLUSIONS
Our findings demonstrate that silibinin induced apoptosis of laryngeal squamous carcinoma cells by a mechanism involving decreased survivin expression, which suggests the possibility that silibinin may be an effective treatment of laryngeal cancers.
Bang
Choong-Il
CI
Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Catholic University of Korea, Seoul, Korea.
Paik
Soon-Young
SY
Sun
Dong-Il
DI
Joo
Young-Hoon
YH
Kim
Min-Sik
MS
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D020944:Silybum marianum; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology; D000077022:Survivin
D000975:Antioxidants; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D012838:Silymarin; D000077022:Survivin; D000077385:Silybin