Abstract
Pectolinarigenin (PEC), a natural flavonoid that is present in citrus fruits, has been reported to exhibit antitumor effects in several cancers. Though the mechanism of PEC-induced cytotoxicity effects has been documented, the proteomic changes that are associated with the cellular response to this flavonoid are poorly understood in gastric cancer cells. In this study, a comparative proteomic analysis was performed to identify proteins associated with PEC-induced cell death in two human gastric cancer cell lines: AGS and MKN-28. Two-dimensional gel electrophoresis (2-DE) revealed a total of 29 and 56 protein spots with significant alteration were screened in AGS and MKN-28 cells respectively. In total, 13 (AGS) and 39 (MKN28) proteins were successfully identified by mass spectrometry from the differential spots and they are known to be involved in signal transduction, apoptosis, transcription and translation, cell structural organization, and metabolism, as is consistent with multiple effects of PEC on tumor cells. Notably, novel target proteins like Probable ATP-dependent RNA helicase DDX4 (DDX4) and E3 ubiquitin-protein ligase LRSAM1 (LRSAM1) along with the commonly differential expressed proteins on both the cell lines that are treated with PEC were confirmed by immunoblotting. The DDX4 accelerates cell cycle progression by abrogating the G2 checkpoint when overexpressed in cancer cells, while the aberrant expression of LRSAM1 may be involved in the cancer pathology. Thus, proteomic analysis provides vital information about target proteins that are important for PEC-induced cell death in gastric cancer cells.
Highlights
Cancer is one of the major public health concerns in both developing and developed countries [1].It is considered as the second leading cause of death worldwide with gastric cancer identified as Nutrients 2018, 10, 1596; doi:10.3390/nu10111596 www.mdpi.com/journal/nutrientsNutrients 2018, 10, 1596 one of the most common recorded cancer cases in the world
It has been reported that PEC was able to decrease the cell viability of AGS and MKN28 cell, human gastric cancer cells through the induction of cell cycle arrest, apoptosis, and autophagy
MTT assay was performed after treatment with PEC at various concentrations (0, 25, 50, 75, 100, and 150 μM) for 24 h (Figure 1) on AGS and MKN28 cells treated with PEC for cell viability
Summary
Cancer is one of the major public health concerns in both developing and developed countries [1].It is considered as the second leading cause of death worldwide with gastric cancer identified as Nutrients 2018, 10, 1596; doi:10.3390/nu10111596 www.mdpi.com/journal/nutrientsNutrients 2018, 10, 1596 one of the most common recorded cancer cases in the world. Cancer is one of the major public health concerns in both developing and developed countries [1]. It is considered as the second leading cause of death worldwide with gastric cancer identified as Nutrients 2018, 10, 1596; doi:10.3390/nu10111596 www.mdpi.com/journal/nutrients. Korea is recognized to have the highest cases of gastric cancer related deaths [2,3]. Proteomic studies could lead to the molecular characterization of cellular event associated with cancer progression, signaling and response to drug treatment. The anti-cancer drug-regulated proteins identified by proteomic analysis can be further characterized as credible drug targets and effectors. The global analysis of protein modification will contribute imperative information to depict the mechanisms of drug action
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