TY - JOUR
T1 - 3,3',4',5'-tetramethoxychalcone inhibits human oral cancer cell proliferation and migration via p53-mediated mitochondrial-dependent apoptosis
AU - Lai, Cheng Kuo
AU - Rao, Yerra Koteswara
AU - Chang, Kai Ruei
AU - Lin, Cheng Wen
AU - Su, Hong Lin
AU - Chang, Chia Shuo
AU - Lai, Chih Ho
AU - Tzeng, Yew Min
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Background/Aim: The current study aimed to identify an attractive target against human oral squamous cell carcinoma (OSCC). Materials and Methods: The effect of 3,3',4',5'-tetramethoxychalcone (TMC) on OSCC cell proliferation, cell-cycle phase distribution, expression of markers of cell apoptosis, and cell migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, western blot, and transwell migration assay, respectively. Results: Experimental results revealed that TMC inhibited the OSCC cell proliferation (fifty percent inhibitory concentrations range=1.0-4.5 μM) by inducing G2/M phase arrest of the cell cycle. TMC caused DNA double-strand breaks, and enhanced expression of caspase-3 and -9, poly (ADP-ribose) polymerase, cytochrome c, calpain-1 and -2, phosphorylation of histone H2AX, phosphorylation of checkpoint kinases 2, p53, BCL2-antagonist/killer and BCL2- associated × protein, while reducing the mitochondrial membrane potential, and expression of B-cell lymphoma-2. In addition, TMC reduced the migration potential of OSCC cells by attenuating the C-C chemokine ligand 5/C-C chemokine receptor type 5 axis. Conclusion: These data indicate that TMC may be considered an interesting target for further development of chemotherapeutic agents against oral cancer.
AB - Background/Aim: The current study aimed to identify an attractive target against human oral squamous cell carcinoma (OSCC). Materials and Methods: The effect of 3,3',4',5'-tetramethoxychalcone (TMC) on OSCC cell proliferation, cell-cycle phase distribution, expression of markers of cell apoptosis, and cell migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, western blot, and transwell migration assay, respectively. Results: Experimental results revealed that TMC inhibited the OSCC cell proliferation (fifty percent inhibitory concentrations range=1.0-4.5 μM) by inducing G2/M phase arrest of the cell cycle. TMC caused DNA double-strand breaks, and enhanced expression of caspase-3 and -9, poly (ADP-ribose) polymerase, cytochrome c, calpain-1 and -2, phosphorylation of histone H2AX, phosphorylation of checkpoint kinases 2, p53, BCL2-antagonist/killer and BCL2- associated × protein, while reducing the mitochondrial membrane potential, and expression of B-cell lymphoma-2. In addition, TMC reduced the migration potential of OSCC cells by attenuating the C-C chemokine ligand 5/C-C chemokine receptor type 5 axis. Conclusion: These data indicate that TMC may be considered an interesting target for further development of chemotherapeutic agents against oral cancer.
KW - 3,3',4',5'-tetramethoxychalcone
KW - Apoptosis
KW - CCL5/CCR5 axis
KW - Cell migration
KW - Cell proliferation
KW - DNA double-strand breaks
KW - Oral cancer
UR - http://www.scopus.com/inward/record.url?scp=84902244981&partnerID=8YFLogxK
M3 - 文章
C2 - 24692714
AN - SCOPUS:84902244981
SN - 0250-7005
VL - 34
SP - 1811
EP - 1820
JO - Anticancer Research
JF - Anticancer Research
IS - 4
ER -
