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      Apoptosis induction and inhibition of invasion and migration in gastric cancer cells by Isoorientin studied using network pharmacology

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          Abstract

          Background

          To investigate the effects of Isoorientin on the apoptosis, proliferation, invasion, and migration of human gastric cancer cells (HGC27 cells).

          Methods

          We used network pharmacology to predict the targets of drugs and diseases. The CCK-8 assay was used to determine the effects of Isoorientin on the proliferation of HGC27 cells. Flow cytometry was employed to analyze the effects of Isoorientin on cell apoptosis and cell cycle distribution of HGC27 cells. Scratch test and transwell chamber test were conducted to assess the effects of Isoorientin on invasion and migration, respectively. Additionally, qPCR and western blot were performed to examine the impact of Isoorientin on apoptosis-related genes and protein expression, respectively.

          Results

          The Isoorientin significantly inhibited the proliferation, migration, and invasion of HGC27 cells compared to the control group. Furthermore, Isoorientin induced apoptosis in HGC27 cells by upregulating the relative expression of Bax and caspase-3 while downregulating the relative expression of p-PI3K, p-AKT, and Bcl-2 proteins.

          Conclusion

          The Isoorientin exhibits inhibitory effects on the proliferation, invasion, and migration of HGC27 cells, and induces apoptosis in gastric cancer cells.

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          Most cited references40

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          Cancer statistics in China, 2015.

          Wanqing Chen, Rongshou Zheng, Peter D Baade … (2016)
          With increasing incidence and mortality, cancer is the leading cause of death in China and is a major public health problem. Because of China's massive population (1.37 billion), previous national incidence and mortality estimates have been limited to small samples of the population using data from the 1990s or based on a specific year. With high-quality data from an additional number of population-based registries now available through the National Central Cancer Registry of China, the authors analyzed data from 72 local, population-based cancer registries (2009-2011), representing 6.5% of the population, to estimate the number of new cases and cancer deaths for 2015. Data from 22 registries were used for trend analyses (2000-2011). The results indicated that an estimated 4292,000 new cancer cases and 2814,000 cancer deaths would occur in China in 2015, with lung cancer being the most common incident cancer and the leading cause of cancer death. Stomach, esophageal, and liver cancers were also commonly diagnosed and were identified as leading causes of cancer death. Residents of rural areas had significantly higher age-standardized (Segi population) incidence and mortality rates for all cancers combined than urban residents (213.6 per 100,000 vs 191.5 per 100,000 for incidence; 149.0 per 100,000 vs 109.5 per 100,000 for mortality, respectively). For all cancers combined, the incidence rates were stable during 2000 through 2011 for males (+0.2% per year; P = .1), whereas they increased significantly (+2.2% per year; P < .05) among females. In contrast, the mortality rates since 2006 have decreased significantly for both males (-1.4% per year; P < .05) and females (-1.1% per year; P < .05). Many of the estimated cancer cases and deaths can be prevented through reducing the prevalence of risk factors, while increasing the effectiveness of clinical care delivery, particularly for those living in rural areas and in disadvantaged populations.
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            Current treatment and recent progress in gastric cancer

            Smita S Joshi, Brian Badgwell (2021)
            Article 0 comments Cited 582 times – based on 0 reviews     Review now
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              Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death.

              Z Oltvai, C Milliman, S Korsmeyer (1993)
              Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (alpha) and two forms of cytosolic protein (beta and gamma). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.
              Article 0 comments Cited 478 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Qin Zhao: qzhao@xzmu.edu.cn
                Journal
                Journal ID (nlm-ta): BMC Complement Med Ther
                Journal ID (iso-abbrev): BMC Complement Med Ther
                Title: BMC Complementary Medicine and Therapies
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2662-7671
                Publication date (Electronic): 19 August 2024
                Publication date PMC-release: 19 August 2024
                Publication date Collection: 2024
                Volume: 24
                Electronic Location Identifier: 309
                Affiliations
                [1 ]Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Materia Medica of Tibetan Medical Research Center of Tibet, School of Medicine, Xizang Minzu University, ( https://ror.org/042170a43) Xianyang, 712082 China
                [2 ]GRID grid.460748.9, ISNI 0000 0004 5346 0588, Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, , Xizang Minzu University, ; Xianyang, 712082 China
                Article
                Publisher ID: 4605
                DOI: 10.1186/s12906-024-04605-z
                PMC ID: 11334567
                PubMed ID: 39160561
                SO-VID: 91f40e3b-28e7-4213-b6a7-5fb4c3ae0215
                Copyright © © The Author(s) 2024
                License:

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                Date received : 4 December 2023
                Date accepted : 5 August 2024
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © BioMed Central Ltd., part of Springer Nature 2024

                Keywords: gastric cancer,isoorientin,network pharmacology,apoptosis,invasion and migration
                Data availability:
                Keywords: gastric cancer, isoorientin, network pharmacology, apoptosis, invasion and migration

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