The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR)
<p dir="ltr">Dysregulated epigenetic modifications are common in lung cancer but have been reversed using demethylating agent like 5-Aza-CdR. 5-Aza-CdR induces/upregulates the NY-ESO-1 antigen in lung cancer. Therefore, we investigated the molecular mechanisms accompanied with the ep...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , , , , , , , , , , , , , |
| منشور في: |
2023
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| الموضوعات: | |
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إضافة وسم
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| _version_ | 1864513529457934336 |
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| author | Varghese P. Inchakalody (14557382) |
| author2 | Shereena P. Hydrose (17821412) Roopesh Krishnankutty (1297770) Maysaloun Merhi (4246147) Lubna Therachiyil (4246156) Varun Sasidharan Nair (5396393) Asma A. Elashi (17821415) Abdul Q. Khan (14153247) Sara Taleb (11264352) Afsheen Raza (492657) Zeenath Safira K.M. Yoosuf (17821418) Queenie Fernandes (14557388) Lobna Al-Zaidan (14557394) Sarra Mestiri (14557379) Nassiba Taib (14557385) Takwa Bedhiafi (14153460) Dina Moustafa (4253005) Laila Assami (17821421) Karama Makni Maalej (17821424) Eyad Elkord (5396390) Shahab Uddin (154400) Ussama Al Homsi (14442150) Said Dermime (79420) |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Varghese P. Inchakalody (14557382) Shereena P. Hydrose (17821412) Roopesh Krishnankutty (1297770) Maysaloun Merhi (4246147) Lubna Therachiyil (4246156) Varun Sasidharan Nair (5396393) Asma A. Elashi (17821415) Abdul Q. Khan (14153247) Sara Taleb (11264352) Afsheen Raza (492657) Zeenath Safira K.M. Yoosuf (17821418) Queenie Fernandes (14557388) Lobna Al-Zaidan (14557394) Sarra Mestiri (14557379) Nassiba Taib (14557385) Takwa Bedhiafi (14153460) Dina Moustafa (4253005) Laila Assami (17821421) Karama Makni Maalej (17821424) Eyad Elkord (5396390) Shahab Uddin (154400) Ussama Al Homsi (14442150) Said Dermime (79420) |
| author_role | author |
| dc.creator.none.fl_str_mv | Varghese P. Inchakalody (14557382) Shereena P. Hydrose (17821412) Roopesh Krishnankutty (1297770) Maysaloun Merhi (4246147) Lubna Therachiyil (4246156) Varun Sasidharan Nair (5396393) Asma A. Elashi (17821415) Abdul Q. Khan (14153247) Sara Taleb (11264352) Afsheen Raza (492657) Zeenath Safira K.M. Yoosuf (17821418) Queenie Fernandes (14557388) Lobna Al-Zaidan (14557394) Sarra Mestiri (14557379) Nassiba Taib (14557385) Takwa Bedhiafi (14153460) Dina Moustafa (4253005) Laila Assami (17821421) Karama Makni Maalej (17821424) Eyad Elkord (5396390) Shahab Uddin (154400) Ussama Al Homsi (14442150) Said Dermime (79420) |
| dc.date.none.fl_str_mv | 2023-04-15T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.ejphar.2023.175612 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/The_molecular_mechanisms_of_apoptosis_accompanied_with_the_epigenetic_regulation_of_the_NY-ESO-1_antigen_in_non-small_lung_cancer_cells_treated_with_decitabine_5-aza-CdR_/25036724 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences Non small lung cancer 5 Aza-CdR Epigenetic regulation NY-ESO-1 Apoptosis Intrinsic and extrinsic apoptotic pathway |
| dc.title.none.fl_str_mv | The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR) |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Dysregulated epigenetic modifications are common in lung cancer but have been reversed using demethylating agent like 5-Aza-CdR. 5-Aza-CdR induces/upregulates the NY-ESO-1 antigen in lung cancer. Therefore, we investigated the molecular mechanisms accompanied with the epigenetic regulation of NY-ESO-1 in 5-Aza-CdR-treated NCI–H1975 cell line. We showed significant induction of the NY-ESO-1 protein (**p < 0.0097) using Cellular ELISA. Bisulfite-sequencing demonstrated 45.6% demethylation efficiency at the NY-ESO-1 gene promoter region and RT-qPCR analysis confirmed the significant induction of NY-ESO-1 at mRNA level (128-fold increase, *p < 0.050). We then investigated the mechanism by which 5-Aza-CdR inhibits cell proliferation in the NCI–H1975 cell line. Upregulation of the death receptors TRAIL (2.04-fold *p < 0.011) and FAS (2.1-fold *p < 0.011) indicate activation of the extrinsic apoptotic pathway. The upregulation of Voltage-dependent anion-selective channel protein 1 (1.9-fold), Major vault protein (1.8-fold), Bax (1.16-fold), and Cytochrome C (1.39-fold) indicate the activation of the intrinsic pathway. We also observed the differential expression of protein Complement C3 (3.3-fold), Destrin (−5.1-fold), Vimentin (−1.7-fold), Peroxiredoxin 4 (−1.6-fold), Fascin (−1.8-fold), Heme oxygenase-2 (−0.67-fold**p < 0.0055), Hsp27 (−0.57-fold**p < 0.004), and Hsp70 (−0.39-fold **p < 0.001), indicating reduced cell growth, cell migration, and metastasis. The upregulation of 40S ribosomal protein S9 (3-fold), 40S ribosomal protein S15 (4.2-fold), 40S ribosomal protein S18 (2.5-fold), and 60S ribosomal protein L22 (4.4-fold) implied the induction of translation machinery. These results reiterate the decisive role of 5-Aza-CdR in lung cancer treatment since it induces the epigenetic regulation of NY-ESO-1 antigen, inhibits cell proliferation, increases apoptosis, and decreases invasiveness.</p><h2>Other Information</h2><p dir="ltr">Published in: European Journal of Pharmacology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.ejphar.2023.175612" target="_blank">https://dx.doi.org/10.1016/j.ejphar.2023.175612</a></p><p dir="ltr">Additional institutions affiliated with: Qatar University Health - QU</p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_2e249e5c442ae209b4d9a931b00cbe36 |
| identifier_str_mv | 10.1016/j.ejphar.2023.175612 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25036724 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR)Varghese P. Inchakalody (14557382)Shereena P. Hydrose (17821412)Roopesh Krishnankutty (1297770)Maysaloun Merhi (4246147)Lubna Therachiyil (4246156)Varun Sasidharan Nair (5396393)Asma A. Elashi (17821415)Abdul Q. Khan (14153247)Sara Taleb (11264352)Afsheen Raza (492657)Zeenath Safira K.M. Yoosuf (17821418)Queenie Fernandes (14557388)Lobna Al-Zaidan (14557394)Sarra Mestiri (14557379)Nassiba Taib (14557385)Takwa Bedhiafi (14153460)Dina Moustafa (4253005)Laila Assami (17821421)Karama Makni Maalej (17821424)Eyad Elkord (5396390)Shahab Uddin (154400)Ussama Al Homsi (14442150)Said Dermime (79420)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesCardiovascular medicine and haematologyOncology and carcinogenesisPharmacology and pharmaceutical sciencesNon small lung cancer5 Aza-CdREpigenetic regulationNY-ESO-1ApoptosisIntrinsic and extrinsic apoptotic pathway<p dir="ltr">Dysregulated epigenetic modifications are common in lung cancer but have been reversed using demethylating agent like 5-Aza-CdR. 5-Aza-CdR induces/upregulates the NY-ESO-1 antigen in lung cancer. Therefore, we investigated the molecular mechanisms accompanied with the epigenetic regulation of NY-ESO-1 in 5-Aza-CdR-treated NCI–H1975 cell line. We showed significant induction of the NY-ESO-1 protein (**p < 0.0097) using Cellular ELISA. Bisulfite-sequencing demonstrated 45.6% demethylation efficiency at the NY-ESO-1 gene promoter region and RT-qPCR analysis confirmed the significant induction of NY-ESO-1 at mRNA level (128-fold increase, *p < 0.050). We then investigated the mechanism by which 5-Aza-CdR inhibits cell proliferation in the NCI–H1975 cell line. Upregulation of the death receptors TRAIL (2.04-fold *p < 0.011) and FAS (2.1-fold *p < 0.011) indicate activation of the extrinsic apoptotic pathway. The upregulation of Voltage-dependent anion-selective channel protein 1 (1.9-fold), Major vault protein (1.8-fold), Bax (1.16-fold), and Cytochrome C (1.39-fold) indicate the activation of the intrinsic pathway. We also observed the differential expression of protein Complement C3 (3.3-fold), Destrin (−5.1-fold), Vimentin (−1.7-fold), Peroxiredoxin 4 (−1.6-fold), Fascin (−1.8-fold), Heme oxygenase-2 (−0.67-fold**p < 0.0055), Hsp27 (−0.57-fold**p < 0.004), and Hsp70 (−0.39-fold **p < 0.001), indicating reduced cell growth, cell migration, and metastasis. The upregulation of 40S ribosomal protein S9 (3-fold), 40S ribosomal protein S15 (4.2-fold), 40S ribosomal protein S18 (2.5-fold), and 60S ribosomal protein L22 (4.4-fold) implied the induction of translation machinery. These results reiterate the decisive role of 5-Aza-CdR in lung cancer treatment since it induces the epigenetic regulation of NY-ESO-1 antigen, inhibits cell proliferation, increases apoptosis, and decreases invasiveness.</p><h2>Other Information</h2><p dir="ltr">Published in: European Journal of Pharmacology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.ejphar.2023.175612" target="_blank">https://dx.doi.org/10.1016/j.ejphar.2023.175612</a></p><p dir="ltr">Additional institutions affiliated with: Qatar University Health - QU</p>2023-04-15T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.ejphar.2023.175612https://figshare.com/articles/journal_contribution/The_molecular_mechanisms_of_apoptosis_accompanied_with_the_epigenetic_regulation_of_the_NY-ESO-1_antigen_in_non-small_lung_cancer_cells_treated_with_decitabine_5-aza-CdR_/25036724CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/250367242023-04-15T03:00:00Z |
| spellingShingle | The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR) Varghese P. Inchakalody (14557382) Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences Non small lung cancer 5 Aza-CdR Epigenetic regulation NY-ESO-1 Apoptosis Intrinsic and extrinsic apoptotic pathway |
| status_str | publishedVersion |
| title | The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR) |
| title_full | The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR) |
| title_fullStr | The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR) |
| title_full_unstemmed | The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR) |
| title_short | The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR) |
| title_sort | The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR) |
| topic | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Cardiovascular medicine and haematology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences Non small lung cancer 5 Aza-CdR Epigenetic regulation NY-ESO-1 Apoptosis Intrinsic and extrinsic apoptotic pathway |