Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1 alpha Degradation
文献类型：期刊论文
| 作者 | Kong, Peizhong1,4; Yu, K. N.5,6; Yang, Miaomiao1,4; Almahi, Waleed Abdelbagi1,4; Nie, Lili1 ; Chen, Guodong1; Han, Wei1,2,3
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| 刊名 | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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| 出版日期 | 2020-05-01 |
| 卷号 | 21 |
| 关键词 | micheliolide radiosensitizer hypoxia-inducible factor-1 alpha vascular endothelial growth factor p53 |
| DOI | 10.3390/ijms21093392 |
| 通讯作者 | Chen, Guodong(c3024034@163.com) ; Han, Wei(hanw@hfcas.ac.cn) |
| 英文摘要 | Micheliolide (MCL) has shown promising anti-inflammatory and anti-tumor efficacy. However, whether and how MCL enhances the sensitivity of non-small-cell lung cancer (NSCLC) to radiotherapy are still unknown. In the present paper, we found that MCL exerted a tumor cell killing effect on NSCLC cells in a dose-dependent manner, and MCL strongly sensitized p53-deficient NSCLC cells, but not the cells with wild-type p53 to irradiation (IR). Meanwhile, MCL markedly inhibited the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) after IR and hypoxic exposure in H1299 and Calu-1 cells rather than in H460 cells. Consistently, radiation- or hypoxia-induced expression of vascular endothelial growth factor (VEGF) was also significantly inhibited by MCL in H1299 and Calu-1 cells, but not in H460 cells. Therefore, inhibition of the HIF-1 alpha pathway might, at least in part, contribute to the radiosensitizing effect of MCL. Further study showed that MCL could accelerate the degradation of HIF-1 alpha through the ubiquitin-proteosome system. In addition, the transfection of wild-type p53 into p53-null cells (H1299) attenuated the effect of MCL on inhibiting HIF-1 alpha expression. These results suggest MCL effectively sensitizes p53-deficient NSCLC cells to IR in a manner of inhibiting the HIF-1 alpha pathway via promoting HIF-1 alpha degradation, and p53 played a negative role in MCL-induced HIF-1 alpha degradation. |
| WOS关键词 | ENDOTHELIAL GROWTH-FACTOR ; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA ; NF-KAPPA-B ; SESQUITERPENE LACTONES ; IN-VITRO ; PARTHENOLIDE ; EXPRESSION ; RADIATION ; INHIBITION ; PATHWAY |
| 资助项目 | Chinese National Natural Science Foundation[81703168] ; Chinese National Natural Science Foundation[U1632145] ; Chinese National Natural Science Foundation[81227902] ; Natural Science Fund of Anhui Province[1608085QH181] ; Key Program of 13th five-year plan, CASHIPS[KP-2017-25] ; CASHIPS Director's Fund[YZJJ2018QN19] ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) ; Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection ; State Key Laboratory in Marine Pollution, City University of Hong Kong[IRF/0024] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000535581700363 |
| 出版者 | MDPI |
| 资助机构 | Chinese National Natural Science Foundation ; Natural Science Fund of Anhui Province ; Key Program of 13th five-year plan, CASHIPS ; CASHIPS Director's Fund ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) ; Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection ; State Key Laboratory in Marine Pollution, City University of Hong Kong |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/103153]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Chen, Guodong; Han, Wei |
| 作者单位 | 1.Chinese Acad Sci, Hefei Inst Phys Sci, Ctr Med Phys & Technol, Anhui Prov Key Lab Med Phys & Technol, Hefei 230031, Peoples R China 2.Soochow Univ, Collaborat Innovat Ctr Radiat Med, Jiangsu Higher Educ Inst, Suzhou 215123, Peoples R China 3.Soochow Univ, Sch Radiol & Interdisciplinary Sci RAD X, Suzhou 215123, Peoples R China 4.Univ Sci & Technol China, Sci Isl Branch, Grad Sch, Hefei 230026, Peoples R China 5.City Univ Hong Kong, Dept Phys, Kowloon Tong, Tat Chee Ave, Hong Kong 999077, Peoples R China 6.City Univ Hong Kong, State Key Lab Marine Pollut, Kowloon Tong, Tat Chee Ave, Hong Kong 999077, Peoples R China |
| 推荐引用方式 GB/T 7714 | Kong, Peizhong,Yu, K. N.,Yang, Miaomiao,et al. Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1 alpha Degradation[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2020,21. |
| APA | Kong, Peizhong.,Yu, K. N..,Yang, Miaomiao.,Almahi, Waleed Abdelbagi.,Nie, Lili.,...&Han, Wei.(2020).Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1 alpha Degradation.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,21. |
| MLA | Kong, Peizhong,et al."Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1 alpha Degradation".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21(2020). |
入库方式： OAI收割
来源：合肥物质科学研究院
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