Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling
Abstract Background Colorectal carcinoma is one of the most deadly cancers that requests effective and safe chemotherapy. Evaluation of natural product-based anticancer drugs as adjuvant treatment with fewer side effects is largely unexplored research fields. Herbal melanin (HM) is an extract of the...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01206-x |
| _version_ | 1818938990456209408 |
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| author | Omar Al-Obeed Adila Salih El-Obeid Sabine Matou-Nasri Mansoor-Ali Vaali-Mohammed Yazeid AlHaidan Mohammed Elwatidy Hamad Al Dosary Zeyad Alehaideb Khayal Alkhayal Adil Haseeb James McKerrow Rehan Ahmad Maha-Hamadien Abdulla |
| author_facet | Omar Al-Obeed Adila Salih El-Obeid Sabine Matou-Nasri Mansoor-Ali Vaali-Mohammed Yazeid AlHaidan Mohammed Elwatidy Hamad Al Dosary Zeyad Alehaideb Khayal Alkhayal Adil Haseeb James McKerrow Rehan Ahmad Maha-Hamadien Abdulla |
| author_sort | Omar Al-Obeed |
| collection | DOAJ |
| description | Abstract Background Colorectal carcinoma is one of the most deadly cancers that requests effective and safe chemotherapy. Evaluation of natural product-based anticancer drugs as adjuvant treatment with fewer side effects is largely unexplored research fields. Herbal melanin (HM) is an extract of the seed coats of Nigella sativa that modulates an inflammatory response through toll-like receptor 4 (TLR4). This TLR4 receptor is also involved in the modulation of apoptosis. We therefore explored the anticancer potential of HM and specifically its effect on the molecular mechanisms underlying adenocarcinoma and metastatic colorectal cancer (mCRC) cell death in vitro. Methods Cell viability was evaluated using the MTT assay. Cellular reactive oxygen species (ROS), glutathione levels, and apoptotic status were assessed using fluorometric and colorimetric detection methods. HM-induced apoptotic and other signaling pathways were investigated using Western blot technology and mitochondrial transition pore assay kit. TLR4 receptor downregulation and blockade were performed using siRNA technology and neutralizing antibody, respectively. Results Our results showed that HM inhibited the proliferation of the colorectal adenocarcinoma HT29 and mCRC SW620 cell lines. Furthermore, HM enhanced ROS production and decreased glutathione levels. HM-induced apoptosis was associated with mitochondrial outer membrane permeability and cytochrome c release, inhibition of the Bcl2 family proteins, and activation of caspase-3/-7. In addition, HM modulated MAPK pathways by activating the JNK pathway and by inhibiting ERK phosphorylation. TLR4 receptor downregulation enhanced HM-induced apoptosis while TLR4 receptor blockade partially alleviated HM-inhibited ERK phosphorylation. Conclusion Altogether, these findings indicate that HM exerts pro-apoptotic effects and inhibits MAPK pathway through TLR4 in mCRC and colorectal adenocarcinoma cells, suggesting HM as a promising natural-based drug for the treatment of colorectal cancer. |
| first_indexed | 2024-12-20T06:16:38Z |
| format | Article |
| id | doaj.art-d180e2b2e34e49b0b7854147914f6c23 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-20T06:16:38Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-d180e2b2e34e49b0b7854147914f6c232022-12-21T19:50:32ZengBMCCancer Cell International1475-28672020-04-0120111710.1186/s12935-020-01206-xHerbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signalingOmar Al-Obeed0Adila Salih El-Obeid1Sabine Matou-Nasri2Mansoor-Ali Vaali-Mohammed3Yazeid AlHaidan4Mohammed Elwatidy5Hamad Al Dosary6Zeyad Alehaideb7Khayal Alkhayal8Adil Haseeb9James McKerrow10Rehan Ahmad11Maha-Hamadien Abdulla12Colorectal Research Chair, Department of Surgery, King Khalid University Hospital and College of Medicine, King Saud UniversityDepartment of Biobank, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health AffairsCell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health AffairsColorectal Research Chair, Department of Surgery, King Khalid University Hospital and College of Medicine, King Saud UniversityCell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health AffairsColorectal Research Chair, Department of Surgery, King Khalid University Hospital and College of Medicine, King Saud UniversityColorectal Research Chair, Department of Surgery, King Khalid University Hospital and College of Medicine, King Saud UniversityCell and Gene Therapy Group, Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health AffairsColorectal Research Chair, Department of Surgery, King Khalid University Hospital and College of Medicine, King Saud UniversityDepartment of Physics, Faculty of Science, University of KhartoumSkaggs School of Pharmacy and Pharmaceutical Chemistry, University of CaliforniaColorectal Research Chair, Department of Surgery, King Khalid University Hospital and College of Medicine, King Saud UniversityColorectal Research Chair, Department of Surgery, King Khalid University Hospital and College of Medicine, King Saud UniversityAbstract Background Colorectal carcinoma is one of the most deadly cancers that requests effective and safe chemotherapy. Evaluation of natural product-based anticancer drugs as adjuvant treatment with fewer side effects is largely unexplored research fields. Herbal melanin (HM) is an extract of the seed coats of Nigella sativa that modulates an inflammatory response through toll-like receptor 4 (TLR4). This TLR4 receptor is also involved in the modulation of apoptosis. We therefore explored the anticancer potential of HM and specifically its effect on the molecular mechanisms underlying adenocarcinoma and metastatic colorectal cancer (mCRC) cell death in vitro. Methods Cell viability was evaluated using the MTT assay. Cellular reactive oxygen species (ROS), glutathione levels, and apoptotic status were assessed using fluorometric and colorimetric detection methods. HM-induced apoptotic and other signaling pathways were investigated using Western blot technology and mitochondrial transition pore assay kit. TLR4 receptor downregulation and blockade were performed using siRNA technology and neutralizing antibody, respectively. Results Our results showed that HM inhibited the proliferation of the colorectal adenocarcinoma HT29 and mCRC SW620 cell lines. Furthermore, HM enhanced ROS production and decreased glutathione levels. HM-induced apoptosis was associated with mitochondrial outer membrane permeability and cytochrome c release, inhibition of the Bcl2 family proteins, and activation of caspase-3/-7. In addition, HM modulated MAPK pathways by activating the JNK pathway and by inhibiting ERK phosphorylation. TLR4 receptor downregulation enhanced HM-induced apoptosis while TLR4 receptor blockade partially alleviated HM-inhibited ERK phosphorylation. Conclusion Altogether, these findings indicate that HM exerts pro-apoptotic effects and inhibits MAPK pathway through TLR4 in mCRC and colorectal adenocarcinoma cells, suggesting HM as a promising natural-based drug for the treatment of colorectal cancer.http://link.springer.com/article/10.1186/s12935-020-01206-xHerbal melaninColorectal cancerProliferationApoptosisReactive oxygen speciesTLR4 receptor |
| spellingShingle | Omar Al-Obeed Adila Salih El-Obeid Sabine Matou-Nasri Mansoor-Ali Vaali-Mohammed Yazeid AlHaidan Mohammed Elwatidy Hamad Al Dosary Zeyad Alehaideb Khayal Alkhayal Adil Haseeb James McKerrow Rehan Ahmad Maha-Hamadien Abdulla Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling Cancer Cell International Herbal melanin Colorectal cancer Proliferation Apoptosis Reactive oxygen species TLR4 receptor |
| title | Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling |
| title_full | Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling |
| title_fullStr | Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling |
| title_full_unstemmed | Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling |
| title_short | Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling |
| title_sort | herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance inducing apoptosis and modulating mapk signaling |
| topic | Herbal melanin Colorectal cancer Proliferation Apoptosis Reactive oxygen species TLR4 receptor |
| url | http://link.springer.com/article/10.1186/s12935-020-01206-x |
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