Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species
Abstract Pancreatic cancer is a highly challenging malignancy with extremely poor prognosis. Cytoglobin (CYGB), a hemeprotein involved in liver fibrosis and cancer development, is expressed in pericytes of all organs. Here, we examined the role of CYGB in the development of pancreatic cancer. CYGB e...
| Những tác giả chính: | , , , , , , , , , , , , , , , , , |
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| Định dạng: | Bài viết |
| Ngôn ngữ: | English |
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Nature Publishing Group
2022-05-01
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| Loạt: | Oncogenesis |
| Truy cập trực tuyến: | https://doi.org/10.1038/s41389-022-00389-4 |
| _version_ | 1828791097538641920 |
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| author | Dinh Viet Hoang Le Thi Thanh Thuy Hoang Hai Vu Ngoc Hieu Kenjiro Kimura Daisuke Oikawa Yoshihiro Ikura Ninh Quoc Dat Truong Huu Hoang Misako Sato-Matsubara Minh Phuong Dong Ngo Vinh Hanh Sawako Uchida-Kobayashi Fuminori Tokunaga Shoji Kubo Naoko Ohtani Katsutoshi Yoshizato Norifumi Kawada |
| author_facet | Dinh Viet Hoang Le Thi Thanh Thuy Hoang Hai Vu Ngoc Hieu Kenjiro Kimura Daisuke Oikawa Yoshihiro Ikura Ninh Quoc Dat Truong Huu Hoang Misako Sato-Matsubara Minh Phuong Dong Ngo Vinh Hanh Sawako Uchida-Kobayashi Fuminori Tokunaga Shoji Kubo Naoko Ohtani Katsutoshi Yoshizato Norifumi Kawada |
| author_sort | Dinh Viet Hoang |
| collection | DOAJ |
| description | Abstract Pancreatic cancer is a highly challenging malignancy with extremely poor prognosis. Cytoglobin (CYGB), a hemeprotein involved in liver fibrosis and cancer development, is expressed in pericytes of all organs. Here, we examined the role of CYGB in the development of pancreatic cancer. CYGB expression appeared predominately in the area surrounding adenocarcinoma and negatively correlated with tumor size in patients with pancreatic cancer. Directly injecting 7, 12-dimethylbenz[a]anthracene into the pancreatic tail in wild-type mice resulted in time-dependent induction of severe pancreatitis, fibrosis, and oxidative damage, which was rescued by Cygb overexpression in transgenic mice. Pancreatic cancer incidence was 93% in wild-type mice but only 55% in transgenic mice. Enhanced CYGB expression in human pancreatic stellate cells in vitro reduced cellular collagen synthesis, inhibited cell activation, increased expression of antioxidant-related genes, and increased CYGB secretion into the medium. Cygb-overexpressing or recombinant human CYGB (rhCYGB) -treated MIA PaCa-2 cancer cells exhibited dose-dependent cell cycle arrest at the G1 phase, diminished cell migration, and reduction in colony formation. RNA sequencing in rhCYGB-treated MIA PaCa-2 cells revealed downregulation of cell cycle and oxidative phosphorylation pathways. An increase in MIA PaCa-2 cell proliferation and reactive oxygen species production by H2O2 challenge was blocked by rhCYGB treatment or Cygb overexpression. PANC-1, OCUP-A2, and BxPC-3 cancer cells showed similar responses to rhCYGB. Known antioxidants N-acetyl cysteine and glutathione also inhibited cancer cell growth. These results demonstrate that CYGB suppresses pancreatic stellate cell activation, pancreatic fibrosis, and tumor growth, suggesting its potential therapeutic application against pancreatic cancer. |
| first_indexed | 2024-12-12T02:44:47Z |
| format | Article |
| id | doaj.art-cd03332a8f1a4b8a91e1f4acb0f2336f |
| institution | Directory Open Access Journal |
| issn | 2157-9024 |
| language | English |
| last_indexed | 2024-12-12T02:44:47Z |
| publishDate | 2022-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Oncogenesis |
| spelling | doaj.art-cd03332a8f1a4b8a91e1f4acb0f2336f2022-12-22T00:41:05ZengNature Publishing GroupOncogenesis2157-90242022-05-0111111310.1038/s41389-022-00389-4Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen speciesDinh Viet Hoang0Le Thi Thanh Thuy1Hoang Hai2Vu Ngoc Hieu3Kenjiro Kimura4Daisuke Oikawa5Yoshihiro Ikura6Ninh Quoc Dat7Truong Huu Hoang8Misako Sato-Matsubara9Minh Phuong Dong10Ngo Vinh Hanh11Sawako Uchida-Kobayashi12Fuminori Tokunaga13Shoji Kubo14Naoko Ohtani15Katsutoshi Yoshizato16Norifumi Kawada17Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Pathobiochemistry, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Pathology, Takatsuki General HospitalDepartment of Pediatrics, Hanoi Medical UniversityDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Pathobiochemistry, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Pathophysiology, Graduate School of Medicine, Osaka Metropolitan UniversityDonated Laboratory for Synthetic Biology, Graduate School of Medicine, Osaka Metropolitan UniversityDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan UniversityAbstract Pancreatic cancer is a highly challenging malignancy with extremely poor prognosis. Cytoglobin (CYGB), a hemeprotein involved in liver fibrosis and cancer development, is expressed in pericytes of all organs. Here, we examined the role of CYGB in the development of pancreatic cancer. CYGB expression appeared predominately in the area surrounding adenocarcinoma and negatively correlated with tumor size in patients with pancreatic cancer. Directly injecting 7, 12-dimethylbenz[a]anthracene into the pancreatic tail in wild-type mice resulted in time-dependent induction of severe pancreatitis, fibrosis, and oxidative damage, which was rescued by Cygb overexpression in transgenic mice. Pancreatic cancer incidence was 93% in wild-type mice but only 55% in transgenic mice. Enhanced CYGB expression in human pancreatic stellate cells in vitro reduced cellular collagen synthesis, inhibited cell activation, increased expression of antioxidant-related genes, and increased CYGB secretion into the medium. Cygb-overexpressing or recombinant human CYGB (rhCYGB) -treated MIA PaCa-2 cancer cells exhibited dose-dependent cell cycle arrest at the G1 phase, diminished cell migration, and reduction in colony formation. RNA sequencing in rhCYGB-treated MIA PaCa-2 cells revealed downregulation of cell cycle and oxidative phosphorylation pathways. An increase in MIA PaCa-2 cell proliferation and reactive oxygen species production by H2O2 challenge was blocked by rhCYGB treatment or Cygb overexpression. PANC-1, OCUP-A2, and BxPC-3 cancer cells showed similar responses to rhCYGB. Known antioxidants N-acetyl cysteine and glutathione also inhibited cancer cell growth. These results demonstrate that CYGB suppresses pancreatic stellate cell activation, pancreatic fibrosis, and tumor growth, suggesting its potential therapeutic application against pancreatic cancer.https://doi.org/10.1038/s41389-022-00389-4 |
| spellingShingle | Dinh Viet Hoang Le Thi Thanh Thuy Hoang Hai Vu Ngoc Hieu Kenjiro Kimura Daisuke Oikawa Yoshihiro Ikura Ninh Quoc Dat Truong Huu Hoang Misako Sato-Matsubara Minh Phuong Dong Ngo Vinh Hanh Sawako Uchida-Kobayashi Fuminori Tokunaga Shoji Kubo Naoko Ohtani Katsutoshi Yoshizato Norifumi Kawada Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species Oncogenesis |
| title | Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species |
| title_full | Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species |
| title_fullStr | Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species |
| title_full_unstemmed | Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species |
| title_short | Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species |
| title_sort | cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species |
| url | https://doi.org/10.1038/s41389-022-00389-4 |
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