Comparative proteomic analysis uncovers potential biomarkers involved in the anticancer effect of Scutellarein in human gastric cancer cells

Saralamma,Venu Venkatarame Gowda; Vetrivel,Preethi; Lee,Ho Jeong; Kim,Seong Min; Ha,Sang Eun; Murugesan,Rajeswari; Kim,Eun Hee; Heo,Jeong Doo; Kim,Gon Sup

doi:10.3892/or.2020.7677

Comparative proteomic analysis uncovers potential biomarkers involved in the anticancer effect of Scutellarein in human gastric cancer cells

Authors:
- Venu Venkatarame Gowda Saralamma
- Preethi Vetrivel
- Ho Jeong Lee
- Seong Min Kim
- Sang Eun Ha
- Rajeswari Murugesan
- Eun Hee Kim
- Jeong Doo Heo
- Gon Sup Kim
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Affiliations: Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongnam 52828, Republic of Korea, Gyeongnam Department of Environment Toxicology and Chemistry, Biological Resources Research Group, Korea Institute of Toxicology, Jinju, Gyeongnam 52834, Republic of Korea, Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, Tamil Nadu 641043, India, Department of Nursing Science, International University of Korea, Jinju, Gyeongnam 52833, Republic of Korea
Published online on: July 7, 2020 https://doi.org/10.3892/or.2020.7677
Pages: 939-958
Copyright: © Saralamma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Scutellarein (SCU), a flavone that belongs to the flavonoid family and abundantly present in Scutellaria baicalensis a flowering plant in the family Lamiaceae, has been reported to exhibit anticancer effects in several cancer cell lines including gastric cancer (GC). Although our previous study documented the mechanisms of Scutellarein‑induced cytotoxic effects, the literature shows that the proteomic changes that are associated with the cellular response to SCU have been poorly understood. To avoid adverse side‑effects and significant toxicity of chemotherapy in patients who react poorly, biomarkers anticipating therapeutic responses are imperative. In the present study, we utilized a comparative proteomic analysis to identify proteins associated with Scutellarein (SCU)‑induced cell death in GC cells (AGS and SNU484), by integrating two‑dimensional gel electrophoresis (2‑DE), mass spectrometry (MS), and bioinformatics to analyze the proteins. Proteomic analysis between SCU‑treated and DMSO (control) samples successfully identified 41 (AGS) and 31 (SNU484) proteins by MALDI‑TOF/MS analysis and protein database search. Comparative proteomics analysis between AGS and SNU484 cells treated with SCU revealed a total of 7 protein identities commonly expressed and western blot analysis validated a subset of identified critical proteins, which were consistent with those of the 2‑DE outcome. Molecular docking studies also confirmed the binding affinity of SCU towards these critical proteins. Phosphatidylinositol 4,5‑bisphosphate 3‑kinase catalytic subunit β isoform (PIK3CB) protein expression was accompanied by a distinct group of cellular functions, including cell growth, and proliferation. Cancerous inhibitor of protein phosphatase 2A (CIP2A), is one of the oncogenic molecules that have been shown to promote tumor growth and resistance to apoptosis and senescence‑inducing therapies. In the present study, both PIK3CB and CIP2A proteins were downregulated in SCU‑treated cells, which boosts our previous results of SCU to induce apoptosis and inhibits GC cell growth by regulating these critical proteins. The comparative proteomic analysis has yielded candidate biomarkers of response to SCU treatment in GC cell models and further validation of these biomarkers will help the future clinical development of SCU as a novel therapeutic drug.

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