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Pharmacological Inhibition of Protein Kinase C Activity Could Induce Apoptosis in Gastric Cancer Cells by Differential Regulation of Apoptosis-Related Genes

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Abstract

The protein kinase C (PKC) signaling pathwayplays a key role in tumor cell proliferation,differentiation, and apoptosis. Gastric cancer usuallypossesses a higher level of PKC activity than normaltissue. We evaluated inhibition of PKC activity inapoptosis induction of gastric cancer cells and theexpression profile of apoptosis-related genes. Gastriccancer cells (AGS) were incubated with two highlyspecific PKC inhibitors (RO-31-8220 and chelerythrine).Cell viability and cell cycle were determined bymethyl-tetrazolium (MTT) assay and flow cytometry,respectively. Apoptosis was characterized by acridineorange staining, DNA gel electrophoresis, and flowcytometry. The expression of p53,p21waf/cip1, c-myc, bcl-2, and bax wasdetermined by western blot. The results showed that bothPKC inhibitors hindered cell growth, arrested cells atG0/G1 phase and induced apoptosis.The protein level of p53, p21waf/cip1, c-myc,and bax was elevated while bcl-2 kept unchangedfollowing drug exposure. In conclusion, PKC inhibitorssuppress growth of gastric cancer cells throughapoptosis induction and cell cycle quiescence, which maybe regulated by differential expression ofapoptosis-related genes.

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Authors
  1. G. H. Zhu
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  2. B. C. Y. Wong
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  3. M. C. Eggo
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  4. S. T. Yuen
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  5. K. C. Lai
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  6. S. K. Lam
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Zhu, G.H., Wong, B.C.Y., Eggo, M.C. et al. Pharmacological Inhibition of Protein Kinase C Activity Could Induce Apoptosis in Gastric Cancer Cells by Differential Regulation of Apoptosis-Related Genes. Dig Dis Sci 44, 2020–2026 (1999). https://doi.org/10.1023/A:1026670301787

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  • DOI: https://doi.org/10.1023/A:1026670301787

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