Capsaicin-induced apoptosis of FaDu human pharyngeal squamous carcinoma cells.
OBJECTIVE
To investigate the anti-tumor effect of capsaicin on human pharyngeal squamous carcinoma cells (FaDu).


METHODS
The expression of apoptosis/cell cycle-related proteins (or genes) was examined by reverse transcriptase- polymerase chain reaction, western blotting and ELISA methods, while the apoptotic cell population, cell morphology and DNA fragmentation levels were assessed using flow cytometry, fluorescence microscopy and agarose gel electrophoresis.


RESULTS
Capsaicin was found to inhibit the growth and proliferation of FaDu cells in a dose- and time-dependent manner. Apoptotic cell death was confirmed by observing increases in nuclear condensation, nuclear DNA fragmentation and sub-G1 DNA content. The observed increase in cytosolic cytochrome c, activation of caspase 3 and PARP (p85) levels following capsaicin treatment indicated that the apoptotic response was mitochondrial pathway-dependent. Gene/protein expression analysis of Bcl-2, Bad and Bax further revealed decreased anti-apoptotic Bcl-2 protein and increased pro-apoptotic Bad/Bax expression. Furthermore, capsaicin suppressed the cell cycle progression at the G1/S phase in FaDu cells by decreasing the expression of the regulators of cyclin B1 and D1, as well as cyclin-dependent protein kinases cdk-1, cdk-2 and cdk-4.


CONCLUSIONS
Our current data show that capsaicin induces apoptosis in FaDu cells and this response is associated with mitochondrial pathways, possibly by mediating cell cycle arrest at G1/S.
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chosun University, Gwangju, Korea.
Thanh-Do
TD
Le
Dongchun
D
Jin
Dong Chun
DC
Jin
Se Ra
SR
Rho
Myung Su
MS
Kim
Rina
R
Yu
Hoon
H
Yoo
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D010610:Pharyngeal Neoplasms / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D002211:Capsaicin