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Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1α Degradation

1
Anhui Province Key Laboratory of Medical Physics and Technology/Center of Medical Physics and Technology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, Hefei 230031, China
2
Science Island Branch of Graduate School, University of Science and Technology of China, Hefei 230026, China
3
Department of Physics, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong 999077, Hong Kong
4
State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong 999077, Hong Kong
5
Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(9), 3392; https://doi.org/10.3390/ijms21093392
Received: 30 April 2020 / Revised: 8 May 2020 / Accepted: 8 May 2020 / Published: 11 May 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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-1α (HIF-1α) 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-1α pathway might, at least in part, contribute to the radiosensitizing effect of MCL. Further study showed that MCL could accelerate the degradation of HIF-1α 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-1α expression. These results suggest MCL effectively sensitizes p53-deficient NSCLC cells to IR in a manner of inhibiting the HIF-1α pathway via promoting HIF-1α degradation, and p53 played a negative role in MCL-induced HIF-1α degradation. View Full-Text
Keywords: micheliolide; radiosensitizer; hypoxia-inducible factor-1α; vascular endothelial growth factor; p53 micheliolide; radiosensitizer; hypoxia-inducible factor-1α; vascular endothelial growth factor; p53
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MDPI and ACS Style

Kong, P.; Yu, K.N.; Yang, M.; Almahi, W.A.; Nie, L.; Chen, G.; Han, W. Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1α Degradation. Int. J. Mol. Sci. 2020, 21, 3392. https://doi.org/10.3390/ijms21093392

AMA Style

Kong P, Yu KN, Yang M, Almahi WA, Nie L, Chen G, Han W. Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1α Degradation. International Journal of Molecular Sciences. 2020; 21(9):3392. https://doi.org/10.3390/ijms21093392

Chicago/Turabian Style

Kong, Peizhong, K.N. Yu, Miaomiao Yang, Waleed A. Almahi, Lili Nie, Guodong Chen, and Wei Han. 2020. "Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1α Degradation" International Journal of Molecular Sciences 21, no. 9: 3392. https://doi.org/10.3390/ijms21093392

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