Regulatory Effects of Apatinib in Combination with Piperine on MDM-2 Gene Expression, Glutathione Peroxidase Activity and Nitric Oxide level as Mechanisms of Cytotoxicity in Colorectal Cancer Cells
Purpose: Apatinib has been utilized in colon cancer therapies but its efficiency and molecularmechanism are not fully understood. Chemotherapy in combination with non-toxic compoundscan be an effective treatment strategy for cancer. Consequently, this study was carried out toevaluate the effects of...
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| Format: | Article |
| Language: | English |
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Tabriz University of Medical Sciences
2022-03-01
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| Series: | Advanced Pharmaceutical Bulletin |
| Subjects: | |
| Online Access: | https://apb.tbzmed.ac.ir/PDF/apb-12-404.pdf |
| _version_ | 1818271788786778112 |
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| author | Mahshid Mohammadian Zakieh Rostamzadeh Khameneh Soraya Emamgholizadeh Minaei Meysam Ebrahimifar Kosar Esgandari |
| author_facet | Mahshid Mohammadian Zakieh Rostamzadeh Khameneh Soraya Emamgholizadeh Minaei Meysam Ebrahimifar Kosar Esgandari |
| author_sort | Mahshid Mohammadian |
| collection | DOAJ |
| description | Purpose: Apatinib has been utilized in colon cancer therapies but its efficiency and molecularmechanism are not fully understood. Chemotherapy in combination with non-toxic compoundscan be an effective treatment strategy for cancer. Consequently, this study was carried out toevaluate the effects of apatinib and piperine on colorectal cancer (CRC) cell line and theirpotential anti-cancerous mechanisms in vitro.Methods: The effects of apatinib and piperine on HCT-116 CRC cells were detected byassessing cell viability using MTT assay. The potential cytotoxic mechanisms of apatinib andpiperine were investigated by evaluating MDM-2 gene expression ratio using real-time PCRassay. Moreover, the glutathione peroxidase (GPX) activity and nitric oxide (NO) levels wereassessed by colorimetric assays.Results: The proliferation rate of CRC cells decreased by increasing the concentrations ofpiperine or apatinib. When HCT-116 cells were treated with different concentrations of apatinibin combination with piperine, the synergistic effects were observed (combination index < 1).In HCT-116 cells treated with apatinib and piperine at the concentrations of 0.5×IC50 and0.2×IC50, the MDM-2 gene expression was downregulated and NO levels increased comparedto the untreated control cells and related single treatments. In addition, GPX activity significantlydecreased in combination treatment at 0.5×IC50 concentration of both agents versus singletreatments.Conclusion: Apatinib in combination with piperine could significantly inhibit the growth ofCRC cells. These cytotoxic effects were induced by regulation of MDM-2 gene expression andinhibition of antioxidant marker. |
| first_indexed | 2024-12-12T21:31:45Z |
| format | Article |
| id | doaj.art-b921906a4d8d40ef9d293c64c1978558 |
| institution | Directory Open Access Journal |
| issn | 2228-5881 2251-7308 |
| language | English |
| last_indexed | 2024-12-12T21:31:45Z |
| publishDate | 2022-03-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | Advanced Pharmaceutical Bulletin |
| spelling | doaj.art-b921906a4d8d40ef9d293c64c19785582022-12-22T00:11:19ZengTabriz University of Medical SciencesAdvanced Pharmaceutical Bulletin2228-58812251-73082022-03-0112240440910.34172/apb.2022.040apb-30698Regulatory Effects of Apatinib in Combination with Piperine on MDM-2 Gene Expression, Glutathione Peroxidase Activity and Nitric Oxide level as Mechanisms of Cytotoxicity in Colorectal Cancer CellsMahshid Mohammadian0Zakieh Rostamzadeh Khameneh1Soraya Emamgholizadeh Minaei2Meysam Ebrahimifar3Kosar Esgandari4Department of Medical Laboratory Sciences, Urmia University of Medical Sciences, Urmia, Iran.Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran.Department of Medical Physics and Imaging, Urmia University of Medical Sciences, Urmia, Iran.Department of Toxicology, Shahreza Azad University, Shahreza, Iran.Department of Medical Physics , Urmia University of Medical Sciences, Urmia, Iran.Purpose: Apatinib has been utilized in colon cancer therapies but its efficiency and molecularmechanism are not fully understood. Chemotherapy in combination with non-toxic compoundscan be an effective treatment strategy for cancer. Consequently, this study was carried out toevaluate the effects of apatinib and piperine on colorectal cancer (CRC) cell line and theirpotential anti-cancerous mechanisms in vitro.Methods: The effects of apatinib and piperine on HCT-116 CRC cells were detected byassessing cell viability using MTT assay. The potential cytotoxic mechanisms of apatinib andpiperine were investigated by evaluating MDM-2 gene expression ratio using real-time PCRassay. Moreover, the glutathione peroxidase (GPX) activity and nitric oxide (NO) levels wereassessed by colorimetric assays.Results: The proliferation rate of CRC cells decreased by increasing the concentrations ofpiperine or apatinib. When HCT-116 cells were treated with different concentrations of apatinibin combination with piperine, the synergistic effects were observed (combination index < 1).In HCT-116 cells treated with apatinib and piperine at the concentrations of 0.5×IC50 and0.2×IC50, the MDM-2 gene expression was downregulated and NO levels increased comparedto the untreated control cells and related single treatments. In addition, GPX activity significantlydecreased in combination treatment at 0.5×IC50 concentration of both agents versus singletreatments.Conclusion: Apatinib in combination with piperine could significantly inhibit the growth ofCRC cells. These cytotoxic effects were induced by regulation of MDM-2 gene expression andinhibition of antioxidant marker.https://apb.tbzmed.ac.ir/PDF/apb-12-404.pdfcolorectal cancerapoptosishct-116 cellsapatinibpiperine |
| spellingShingle | Mahshid Mohammadian Zakieh Rostamzadeh Khameneh Soraya Emamgholizadeh Minaei Meysam Ebrahimifar Kosar Esgandari Regulatory Effects of Apatinib in Combination with Piperine on MDM-2 Gene Expression, Glutathione Peroxidase Activity and Nitric Oxide level as Mechanisms of Cytotoxicity in Colorectal Cancer Cells Advanced Pharmaceutical Bulletin colorectal cancer apoptosis hct-116 cells apatinib piperine |
| title | Regulatory Effects of Apatinib in Combination with Piperine on MDM-2 Gene Expression, Glutathione Peroxidase Activity and Nitric Oxide level as Mechanisms of Cytotoxicity in Colorectal Cancer Cells |
| title_full | Regulatory Effects of Apatinib in Combination with Piperine on MDM-2 Gene Expression, Glutathione Peroxidase Activity and Nitric Oxide level as Mechanisms of Cytotoxicity in Colorectal Cancer Cells |
| title_fullStr | Regulatory Effects of Apatinib in Combination with Piperine on MDM-2 Gene Expression, Glutathione Peroxidase Activity and Nitric Oxide level as Mechanisms of Cytotoxicity in Colorectal Cancer Cells |
| title_full_unstemmed | Regulatory Effects of Apatinib in Combination with Piperine on MDM-2 Gene Expression, Glutathione Peroxidase Activity and Nitric Oxide level as Mechanisms of Cytotoxicity in Colorectal Cancer Cells |
| title_short | Regulatory Effects of Apatinib in Combination with Piperine on MDM-2 Gene Expression, Glutathione Peroxidase Activity and Nitric Oxide level as Mechanisms of Cytotoxicity in Colorectal Cancer Cells |
| title_sort | regulatory effects of apatinib in combination with piperine on mdm 2 gene expression glutathione peroxidase activity and nitric oxide level as mechanisms of cytotoxicity in colorectal cancer cells |
| topic | colorectal cancer apoptosis hct-116 cells apatinib piperine |
| url | https://apb.tbzmed.ac.ir/PDF/apb-12-404.pdf |
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