Tumor Biology

, Volume 35, Issue 10, pp 10051–10056 | Cite as

Anticancer bioactive peptide (ACBP) inhibits gastric cancer cells by upregulating growth arrest and DNA damage-inducible gene 45A (GADD45A)

Research Article

Abstract

Recently, we reported that anticancer bioactive peptide (ACBP), purified from goat spleens immunized with human gastric cancer extracts, significantly inhibited gastric cancer cells in vitro and gastric tumors in vivo via repressing cell growth and promoting apoptosis, making it a promising potential biological anticancer drug. However, it is not known what genes are functionally required for the ACBP effects. Here, we first found that two tumor suppressor genes, cyclin-dependent kinase inhibitor 2B (CDKN2B) and growth arrest and DNA damage-inducible alpha (GADD45A), were upregulated significantly in the cells with ACBP treatment by microarray screening and the findings were validated by real-time RT-PCR. Next, GADD45A mRNA and protein expressions were downregulated in the gastric cancer cells by lentivirus-mediated RNAi; then, cell viability, cell cycle, and apoptosis were assayed by MTT and flow cytometry. Interestingly, our results indicated that cell viability was not dependent on GADD45A without ACBP treatment; however, cell sensitivity to ACBP was significantly decreased in ACBP-treated gastric cancer cells with GADD45A downregulation. Therefore, we demonstrate that GADD45A was functionally required for ACBP to inhibit gastric cancer cells, suggesting that GADD45A may become a biomarker for ACBP sensitivity. Our findings have significant implications on the molecular mechanism understanding, biomarker development, and anticancer drug development of ACBP.

Keywords

Anticancer bioactive peptide Gastric cancer Cell viability Apoptosis Cell cycle CDKN2B GADD45A 

Notes

Acknowledgment

This research was supported by the National Natural Science Foundation (81160254).

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Clinical Medicine Research Center of the Affiliated HospitalInner Mongolia Medical UniversityHohhotChina
  2. 2.Biomolecular Function Discovery Division, Bioinformatics Institute, Biomedical Sciences InstitutesAgency for Science, Technology and Research (A*STAR)SingaporeSingapore
  3. 3.Department of Biochemistry and Molecular Biology, Shanghai Medical CollegeFudan UniversityShanghaiPeople’s Republic of China

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