Cell growth regulation through apoptosis by activin in human gastric cancer SNU-16 cell lines.
Activin has a wide variety of biological functions, including the regulation of cell proliferation and inhibition of tumor cells. We have studied whether activin regulates apoptosis by investigating the effects of activin A on cell proliferation, cell cycle, apoptosis, apoptosis-related gene expression, and caspase activity in SNU-16 cells. Activin A significantly inhibited DNA synthesis and growth suppression in a time-dependent manner in SNU-16 cells. Apoptosis fraction was increased at cell cycle with an accompanying DNA fragmentation. Activin A resulted in a significant time-dependent decrease in Bcl-2 mRNA levels and increase in caspase-3 mRNA levels in SNU-16 cells. No significant difference was observed in Bax mRNA levels. Exposure of cells to activin A induced caspase-3, -8 and -9 activation in SNU-16 cells. Furthermore, co-treatment of activin with the pan-caspase inhibitor Z-VAD-FMK, caspase-3 inhibitor Z-DEVE-FMK, caspase-8 inhibitor Z-IETD-FMK, and caspase-9-inhibitor Z-LEHD-FMK blocked apoptosis of SNU-16 cells. Taken together, our results revealed that activin inhibits the growth of SNU-16 cells by inducing apoptosis through caspase activation.
Kim
Young Il
YI
East-West Medical Research Institute, Kyung Hee University, Seoul 130-702, Korea.
Kim
Byung-Ho
BH
Khang
Inkoo
I
Cho
Byung-Nam
BN
Lee
Ha Kyu
HK
D028341:Activins / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C422405:activin A; D051028:bcl-2-Associated X Protein; D028341:Activins; D020169:Caspases