Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer
Colorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)—a free-radical gas—plus its endogenous producer NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/7/1881 |
| _version_ | 1797562665304850432 |
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| author | Hao Wang Liye Wang Zuoxu Xie Shuang Zhou Yan Li Yue Zhou Meiyan Sun |
| author_facet | Hao Wang Liye Wang Zuoxu Xie Shuang Zhou Yan Li Yue Zhou Meiyan Sun |
| author_sort | Hao Wang |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)—a free-radical gas—plus its endogenous producer NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor) in cancers. Endogenous levels of NO promote colon neoplasms, whereas exogenously sustained doses lead to cytotoxic functions. Importantly, NO has been implicated as an essential mediator in many signaling pathways in CRC, such as the Wnt/β-catenin and extracellular-signal-regulated kinase (ERK) pathways, which are closely associated with cancer initiation, metastasis, inflammation, and chemo-/radio-resistance. Therefore, NO/NOS have been proposed as promising targets in the regulation of CRC carcinogenesis. Clinically relevant NO-donating agents have been developed for CRC therapy to deliver a high level of NO to tumor sites. Notably, inducible NOS (iNOS) is ubiquitously over-expressed in inflammatory-associated colon cancer. The development of iNOS inhibitors contributes to targeted therapies for CRC with clinical benefits. In this review, we summarize the multifaceted mechanisms of NO-mediated networks in several hallmarks of CRC. We review the clinical manifestation and limitations of NO donors and NOS inhibitors in clinical trials. We also discuss the possible directions of NO/NOS therapies in the immediate future. |
| first_indexed | 2024-03-10T18:31:08Z |
| format | Article |
| id | doaj.art-feef4b1889d74806ac3925ff5b1e5219 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:31:08Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-feef4b1889d74806ac3925ff5b1e52192023-11-20T06:36:40ZengMDPI AGCancers2072-66942020-07-01127188110.3390/cancers12071881Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon CancerHao Wang0Liye Wang1Zuoxu Xie2Shuang Zhou3Yan Li4Yue Zhou5Meiyan Sun6College of Laboratory Medicine, Jilin Medical University, Jilin 132013, ChinaDepartment of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, TX, 77204, USADepartment of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, TX, 77204, USADepartment of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, TX, 77204, USADepartment of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, TX, 77204, USADepartment of Statistics, North Dakota University, Fargo, ND 58105, USACollege of Laboratory Medicine, Jilin Medical University, Jilin 132013, ChinaColorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)—a free-radical gas—plus its endogenous producer NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor) in cancers. Endogenous levels of NO promote colon neoplasms, whereas exogenously sustained doses lead to cytotoxic functions. Importantly, NO has been implicated as an essential mediator in many signaling pathways in CRC, such as the Wnt/β-catenin and extracellular-signal-regulated kinase (ERK) pathways, which are closely associated with cancer initiation, metastasis, inflammation, and chemo-/radio-resistance. Therefore, NO/NOS have been proposed as promising targets in the regulation of CRC carcinogenesis. Clinically relevant NO-donating agents have been developed for CRC therapy to deliver a high level of NO to tumor sites. Notably, inducible NOS (iNOS) is ubiquitously over-expressed in inflammatory-associated colon cancer. The development of iNOS inhibitors contributes to targeted therapies for CRC with clinical benefits. In this review, we summarize the multifaceted mechanisms of NO-mediated networks in several hallmarks of CRC. We review the clinical manifestation and limitations of NO donors and NOS inhibitors in clinical trials. We also discuss the possible directions of NO/NOS therapies in the immediate future.https://www.mdpi.com/2072-6694/12/7/1881nitric oxideNONO synthasesNOSiNOStargeted therapy |
| spellingShingle | Hao Wang Liye Wang Zuoxu Xie Shuang Zhou Yan Li Yue Zhou Meiyan Sun Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer Cancers nitric oxide NO NO synthases NOS iNOS targeted therapy |
| title | Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer |
| title_full | Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer |
| title_fullStr | Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer |
| title_full_unstemmed | Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer |
| title_short | Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer |
| title_sort | nitric oxide no and no synthases nos based targeted therapy for colon cancer |
| topic | nitric oxide NO NO synthases NOS iNOS targeted therapy |
| url | https://www.mdpi.com/2072-6694/12/7/1881 |
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