Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa Cells
Host defense caerin 1.1 and 1.9 peptides, isolated from the glandular secretion of Australian tree frogs, the genus Litoria, have been previously shown to have multiple biological activities, including the inhibition of human papillomavirus (HPV) 16 early protein E7 transformed murine as well as hum...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-07-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00676/full |
| _version_ | 1811219982767357952 |
|---|---|
| author | Guoying Ni Guoying Ni Guoying Ni Shu Chen Mo Chen Jialing Wu Binbin Yang Binbin Yang Jianwei Yuan Shelley F. Walton Hejie Li Hejie Li Ming Q. Wei Yuejian Wang Guoqiang Chen Xiaosong Liu Xiaosong Liu Xiaosong Liu Tianfang Wang |
| author_facet | Guoying Ni Guoying Ni Guoying Ni Shu Chen Mo Chen Jialing Wu Binbin Yang Binbin Yang Jianwei Yuan Shelley F. Walton Hejie Li Hejie Li Ming Q. Wei Yuejian Wang Guoqiang Chen Xiaosong Liu Xiaosong Liu Xiaosong Liu Tianfang Wang |
| author_sort | Guoying Ni |
| collection | DOAJ |
| description | Host defense caerin 1.1 and 1.9 peptides, isolated from the glandular secretion of Australian tree frogs, the genus Litoria, have been previously shown to have multiple biological activities, including the inhibition of human papillomavirus (HPV) 16 early protein E7 transformed murine as well as human cancerous cell proliferation both in vitro and in vivo. However, the mechanism underlying their anti-proliferative activities against HPV18+ cervical cancer HeLa cells remains unknown. This study comparatively investigated the anti-proliferation on HeLa cells by caerin 1.1, 1.9, and their mixture, followed by confocal microscopy examination to assess the cellular intake of the peptides. Tandem mass tag labeling proteomics was employed to reveal the proteins that were significantly regulated by the peptide treatment in cells and cell growth environment, to elucidate the signaling pathways that were modulated. Western blot was performed to confirm the modulation of the pathways. Both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect compared to untreated and control peptide. They entered the cells with different magnitudes. Intensive protein-protein interaction was detected among significantly upregulated proteins. Translation, folding and localization of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptotic signaling was suggested as a result of tumor necrosis factor-α (TNF-α) pathway activation, indicated by the dose-dependent elevated levels of caspase 3 and caspase 9. The epidermal growth factor receptor and androgen receptor pathways appeared inhibited by the peptides. Moreover, the activation of T-cell receptor derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of HeLa cells. Our results indicate that caerin 1.1 and 1.9 mediate apoptotic signals of HeLa cells and may subsequently enhances adaptive T cell immune responses. |
| first_indexed | 2024-04-12T07:34:49Z |
| format | Article |
| id | doaj.art-a440bb55b4dd4979b4d12dceee071877 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T07:34:49Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-a440bb55b4dd4979b4d12dceee0718772022-12-22T03:41:58ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-07-01810.3389/fcell.2020.00676544698Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa CellsGuoying Ni0Guoying Ni1Guoying Ni2Shu Chen3Mo Chen4Jialing Wu5Binbin Yang6Binbin Yang7Jianwei Yuan8Shelley F. Walton9Hejie Li10Hejie Li11Ming Q. Wei12Yuejian Wang13Guoqiang Chen14Xiaosong Liu15Xiaosong Liu16Xiaosong Liu17Tianfang Wang18Cancer Research Institute, First People’s Hospital of Foshan, Foshan, ChinaGenecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, AustraliaThe First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, ChinaCancer Research Institute, First People’s Hospital of Foshan, Foshan, ChinaMenzies Health Institute Queensland and School of Medical Science, Griffith University, Southport, QLD, AustraliaCancer Research Institute, First People’s Hospital of Foshan, Foshan, ChinaMenzies Health Institute Queensland and School of Medical Science, Griffith University, Southport, QLD, AustraliaDepartment of Laboratory Medicine, Institute of Nanomedicine Technology, Weifang Medical University, Weifang, ChinaThe First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, ChinaGenecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, AustraliaGenecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, AustraliaDepartment of Mechanical and Biofunctional System, Institute of Industrial Science, The University of Tokyo, Tokyo, JapanMenzies Health Institute Queensland and School of Medical Science, Griffith University, Southport, QLD, AustraliaCancer Research Institute, First People’s Hospital of Foshan, Foshan, ChinaCancer Research Institute, First People’s Hospital of Foshan, Foshan, ChinaCancer Research Institute, First People’s Hospital of Foshan, Foshan, ChinaGenecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, AustraliaThe First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, ChinaGenecology Research Centre, University of the Sunshine Coast, Maroochydore, QLD, AustraliaHost defense caerin 1.1 and 1.9 peptides, isolated from the glandular secretion of Australian tree frogs, the genus Litoria, have been previously shown to have multiple biological activities, including the inhibition of human papillomavirus (HPV) 16 early protein E7 transformed murine as well as human cancerous cell proliferation both in vitro and in vivo. However, the mechanism underlying their anti-proliferative activities against HPV18+ cervical cancer HeLa cells remains unknown. This study comparatively investigated the anti-proliferation on HeLa cells by caerin 1.1, 1.9, and their mixture, followed by confocal microscopy examination to assess the cellular intake of the peptides. Tandem mass tag labeling proteomics was employed to reveal the proteins that were significantly regulated by the peptide treatment in cells and cell growth environment, to elucidate the signaling pathways that were modulated. Western blot was performed to confirm the modulation of the pathways. Both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect compared to untreated and control peptide. They entered the cells with different magnitudes. Intensive protein-protein interaction was detected among significantly upregulated proteins. Translation, folding and localization of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptotic signaling was suggested as a result of tumor necrosis factor-α (TNF-α) pathway activation, indicated by the dose-dependent elevated levels of caspase 3 and caspase 9. The epidermal growth factor receptor and androgen receptor pathways appeared inhibited by the peptides. Moreover, the activation of T-cell receptor derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of HeLa cells. Our results indicate that caerin 1.1 and 1.9 mediate apoptotic signals of HeLa cells and may subsequently enhances adaptive T cell immune responses.https://www.frontiersin.org/article/10.3389/fcell.2020.00676/fullcaerin peptideHeLa cellapoptosisTNF-α signaling pathwayTMT labelingproteomics |
| spellingShingle | Guoying Ni Guoying Ni Guoying Ni Shu Chen Mo Chen Jialing Wu Binbin Yang Binbin Yang Jianwei Yuan Shelley F. Walton Hejie Li Hejie Li Ming Q. Wei Yuejian Wang Guoqiang Chen Xiaosong Liu Xiaosong Liu Xiaosong Liu Tianfang Wang Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa Cells Frontiers in Cell and Developmental Biology caerin peptide HeLa cell apoptosis TNF-α signaling pathway TMT labeling proteomics |
| title | Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa Cells |
| title_full | Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa Cells |
| title_fullStr | Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa Cells |
| title_full_unstemmed | Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa Cells |
| title_short | Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa Cells |
| title_sort | host defense peptides caerin 1 1 and 1 9 stimulate tnf alpha dependent apoptotic signals in human cervical cancer hela cells |
| topic | caerin peptide HeLa cell apoptosis TNF-α signaling pathway TMT labeling proteomics |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00676/full |
| work_keys_str_mv | AT guoyingni hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT guoyingni hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT guoyingni hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT shuchen hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT mochen hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT jialingwu hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT binbinyang hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT binbinyang hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT jianweiyuan hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT shelleyfwalton hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT hejieli hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT hejieli hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT mingqwei hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT yuejianwang hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT guoqiangchen hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT xiaosongliu hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT xiaosongliu hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT xiaosongliu hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells AT tianfangwang hostdefensepeptidescaerin11and19stimulatetnfalphadependentapoptoticsignalsinhumancervicalcancerhelacells |