Citation: Hao Ma, Yuelin Wu, Wannian Zhang, Huojun Zhang, Zhenyuan Miao, Chunlin Zhuang. Radiosensitization of human pancreatic cancer by piperlongumine analogues[J]. Chinese Chemical Letters, ;2021, 32(3): 1197-1201. doi: 10.1016/j.cclet.2020.08.049 shu

Radiosensitization of human pancreatic cancer by piperlongumine analogues

Hao Ma ^{a, e} ,
Yuelin Wu ^d ,
Wannian Zhang ^{a, c} ,
Huojun Zhang ^b ,
Zhenyuan Miao ^{a, *,} ,
Chunlin Zhuang ^{a, c, *,}

a.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China
b.
Department of Radiation Oncology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai 200433, China
c.
School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China
d.
School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
e.
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

miaozhenyuan@hotmail.com

zclnathan@163.com

Received Date: 28 May 2020
Revised Date: 31 July 2020
Accepted Date: 30 August 2020
Available Online: 2 September 2020

Figures(3)

Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by 2 months in combination with gemcitabine. However, prognosis and survival improvement remain unsatisfactory, and effective therapies are urgently needed. Piperlongumine has been demonstrated to have therapeutic potentials against various cancers. In this study, we synthesized a series of piperlongumine derivatives and provided evidence that piperlongumine derivatives could be used as effective radiosensitizers in pancreatic cancer. Two compounds enhanced the radiosensitivity of Panc-1 and SW1990 cells. In a pancreatic bi-flank xenograft tumor model, they significantly inhibited tumor growth. Piperlongumine derivatives could induce reactive oxygen species (ROS) expression and regulate the Keap1-Nrf2 protective pathway with enhancement of radiation-induced DNA damage, G2/M-phase cell cycle arrest, and apoptosis. Collectively, our data offer a proof of concept for the use of piperlongumine derivatives as a novel class of radiosensitizers for the treatment of pancreatic cancer.
- Piperlongumine,
- Pancreatic cancer,
- Radiosensitization,
- Sensitivity enhancement ratio (SER),
- Reactive oxygen species (ROS),
- Keap1-Nrf2,
- Bi-flank xenograft tumor model
1. [1]
  X. Zhang, Q. Liu, Q. Liao, Y. Zhao, J. Cancer 11(2020) 2749-2758. doi: 10.7150/jca.37445
2. [2]
  J. Dai, Y. Zhang, H. Li, et al., Chin. Chem. Lett. 28(2017) 531-536. doi: 10.1016/j.cclet.2016.11.008
3. [3]
  P.A. Philip, J. Lacy, F. Portales, et al., Lancet Gastroenterol. Hepatol. 5(2020) 285-294. doi: 10.1016/S2468-1253(19)30327-9
4. [4]
  A.S. Azmi, H.Y. Khan, I. Muqbil, et al., Clin. Cancer Res. 26(2020) 1338-1348. doi: 10.1158/1078-0432.CCR-19-1728
5. [5]
  U.M. Vogl, H. Andalibi, A. Klaus, et al., BMC Cancer 19(2019) 28-36. doi: 10.1186/s12885-018-5240-6
6. [6]
  I.R. Cho, H. Kang, J.H. Jo, et al., World J. Gastrointest. Oncol. 12(2020) 182-194.
7. [7]
  T. Kamisawa, L.D. Wood, T. Itoi, K. Takaori, Lancet 388(2016) 73-85. doi: 10.1016/S0140-6736(16)00141-0
8. [8]
  M. Suker, B.R. Beumer, E. Sadot, et al., Lancet Oncol. 17(2016) 801-810. doi: 10.1016/S1470-2045(16)00172-8
9. [9]
  T. Conroy, J.B. Bachet, A. Ayav, et al., Eur. J. Cancer 57(2016) 10-22. doi: 10.1016/j.ejca.2015.12.026
10. [10]
  N.H. Tran, V. Sahai, K.A. Griffith, et al., Int. J. Radiat. Oncol. Biol. Phys. 106(2020) 124-133. doi: 10.1016/j.ijrobp.2019.08.057
11. [11]
  A. Chatterjee, C.P. Dutta, Sci. Cult. 29(1963) 568-570.
12. [12]
  S. Prasad, A.K. Tyagi, Curr. Pharm. Des. 22(2016) 4151-4159. doi: 10.2174/1381612822666160601103027
13. [13]
  J. Zhou, Z. Huang, X. Ni, C. Lv, Toxicol. In Vitro 65(2020) 104775. doi: 10.1016/j.tiv.2020.104775
14. [14]
  C. Zhuang, W. Zhang, C. Sheng, et al., Chem. Rev. 117(2017) 7762-7810. doi: 10.1021/acs.chemrev.7b00020
15. [15]
  Y. Wu, X. Min, C. Zhuang, et al., Eur. J. Med. Chem. 82(2014) 545-551. doi: 10.1016/j.ejmech.2014.05.070
16. [16]
  Z. Wang, S.T. Lai, N.Y. Ma, et al., Cancer Lett. 369(2015) 192-201. doi: 10.1016/j.canlet.2015.08.015
17. [17]
  D. Wei, H. Li, J. Yu, et al., Cancer Res. 72(2012) 282-293. doi: 10.1158/0008-5472.CAN-11-2866
18. [18]
  D. Schmoll, C.K. Engel, H. Glombik, Drug Discov, Today 24(2017) 11-17. doi: 10.1016/j.ddtec.2017.10.001
19. [19]
  M.D. Xu, S.L. Liu, B.B. Zheng, et al., Pancreatology 3903(2018) 30645-30648.
20. [20]
  J.B. Baell, G.A. Holloway, J. Med. Chem. 53(2010) 2719-2740. doi: 10.1021/jm901137j
21. [21]
  S.J. Capuzzi, E.N. Muratov, A. Tropsha, J. Chem. Inf. Model. 57(2017) 417-427. doi: 10.1021/acs.jcim.6b00465
22. [22]
  B. Zhou, X. Yu, C. Zhuang, et al., ChemMedChem 11(2016) 1436-1445. doi: 10.1002/cmdc.201600150
23. [23]
  J. Lin, X.D. Li, Chin. Chem. Lett. 29(2018) 1051-1057. doi: 10.1016/j.cclet.2018.05.017
24. [24]
  H. Chen, Y. Jiang, Y. Zhang, et al., Chin. Chem. Lett. 28(2017) 913-918. doi: 10.1016/j.cclet.2016.11.027
25. [25]
  F. Salehi, H. Behboudi, G. Kavoosi, S.K. Ardestani, Sci. Rep. 8(2018) 13902. doi: 10.1038/s41598-018-32308-2
1. [1]
  Yuanyuan Zeng , Fang Liu , Jun Wang , Bianfei Shao , Tao He , Zhongzheng Xiang , Yan Wang , Shunyao Zhu , Tian Yang , Siting Yu , Changyang Gong , Lei Liu . Fisetin micelles precisely exhibit a radiosensitization effect by inhibiting PDGFRβ/STAT1/STAT3/Bcl-2 signaling pathway in tumor. Chinese Chemical Letters, 2025, 36(2): 109734-. doi: 10.1016/j.cclet.2024.109734
2. [2]
  Yuanyi Zhou , Ke Ma , Jinfeng Liu , Zirun Zheng , Bo Hu , Yu Meng , Zhizhong Li , Mingshan Zhu . Is reactive oxygen species the only way for cancer inhibition over single atom nanomedicine? Autophagy regulation also works. Chinese Chemical Letters, 2024, 35(6): 109056-. doi: 10.1016/j.cclet.2023.109056
3. [3]
  Ping Song , Nan Zhang , Jie Wang , Rui Yan , Zhiqiang Wang , Yingxue Jin . Experimental Teaching Design on Synthesis and Antitumor Activity Study of Cu-Pyropheophorbide-a Methyl Ester. University Chemistry, 2024, 39(6): 278-286. doi: 10.3866/PKU.DXHX202310087
4. [4]
  Zhongyu Wang , Lijun Wang , Huaixin Zhao . DNA-based nanosystems to generate reactive oxygen species for nanomedicine. Chinese Chemical Letters, 2024, 35(11): 109637-. doi: 10.1016/j.cclet.2024.109637
5. [5]
  Chi Zhang , Ning Ding , Yuwei Pan , Lichun Fu , Ying Zhang . The degradation pathways of contaminants by reactive oxygen species generated in the Fenton/Fenton-like systems. Chinese Chemical Letters, 2024, 35(10): 109579-. doi: 10.1016/j.cclet.2024.109579
6. [6]
  Yueying Yang , Huiru Xie , Xinbo Yu , Yang Liu , Hui Wang , Hua Li , Lixia Chen . Design, synthesis and evaluation of the first DYRK1A degrader for promoting the proliferation of pancreatic β-cells. Chinese Chemical Letters, 2024, 35(11): 109570-. doi: 10.1016/j.cclet.2024.109570
7. [7]
  Xiangqian Cao , Chenkai Yang , Xiaodong Zhu , Mengxin Zhao , Yilin Yan , Zhengnan Huang , Jinming Cai , Jingming Zhuang , Shengzhou Li , Wei Li , Bing Shen . Synergistic enhancement of chemotherapy for bladder cancer by photothermal dual-sensitive nanosystem with gold nanoparticles and PNIPAM. Chinese Chemical Letters, 2024, 35(8): 109199-. doi: 10.1016/j.cclet.2023.109199
8. [8]
  Han Han , Bi-Te Chen , Jia-Rong Ding , Jin-Ming Si , Tian-Jiao Zhou , Yi Wang , Lei Xing , Hu-Lin Jiang . A PDGFRβ-targeting nanodrill system for pancreatic fibrosis therapy. Chinese Chemical Letters, 2024, 35(10): 109583-. doi: 10.1016/j.cclet.2024.109583
9. [9]
  Xueying Shi , Xiaoxuan Zhou , Bing Xiao , Hongxia Xu , Wei Zhang , Hongjie Hu , Shiqun Shao , Zhuxian Zhou , Youqing Shen , Xiaodan Xu , Jianbin Tang . A β-lapachone-loaded iron-polyphenol nanocomplex enhances chemodynamic therapy through cascade amplification of ROS in tumor. Chinese Chemical Letters, 2025, 36(5): 110178-. doi: 10.1016/j.cclet.2024.110178
10. [10]
  Meiling Zhao , Yao Lu , Yutao Zhang , Haoyun Xue , Zhiqian Guo . Ultra-high signal-to-noise ratio near-infrared chemiluminescent probe for in vivo sensing singlet oxygen. Chinese Chemical Letters, 2025, 36(5): 110105-. doi: 10.1016/j.cclet.2024.110105
11. [11]
  Yuanzheng Wang , Chen Zhang , Shuyan Han , Xiaoli Kong , Changyun Quan , Jun Wu , Wei Zhang . Cancer cell membrane camouflaged biomimetic gelatin-based nanogel for tumor inhibition. Chinese Chemical Letters, 2024, 35(11): 109578-. doi: 10.1016/j.cclet.2024.109578
12. [12]
  Yanfei Liu , Yaqin Hu , Yifu Tan , Qiwen Chen , Zhenbao Liu . Tumor acidic microenvironment activatable DNA nanostructure for precise cancer cell targeting and inhibition. Chinese Chemical Letters, 2025, 36(1): 110289-. doi: 10.1016/j.cclet.2024.110289
13. [13]
  Yanhua Chen , Xian Ding , Jun Zhou , Zhaoying Wang , Yunhai Bo , Ying Hu , Qingce Zang , Jing Xu , Ruiping Zhang , Jiuming He , Fen Yang , Zeper Abliz . Plasma metabolomics combined with mass spectrometry imaging reveals crosstalk between tumor and plasma in gastric cancer genesis and metastasis. Chinese Chemical Letters, 2025, 36(1): 110351-. doi: 10.1016/j.cclet.2024.110351
14. [14]
  Shuang Liang , Jianjun Yao , Dan Liu , Mengli Zhou , Yong Cui , Zhaohui Wang . Tumor-responsive covalent organic polymeric nanoparticles enhancing STING activation for cancer immunotherapy. Chinese Chemical Letters, 2025, 36(3): 109856-. doi: 10.1016/j.cclet.2024.109856
15. [15]
  Yunyan Li , Zimin Cai , Zhicheng Wang , Sifeng Zhu , Wendian Liu , Cheng Wang . Construction of biomimetic hybrid nanovesicles based on M1 macrophage-derived exosomes for therapy of cancer. Chinese Chemical Letters, 2025, 36(4): 109942-. doi: 10.1016/j.cclet.2024.109942
16. [16]
  Honghao Sun , Huimin Zhao , Ronghui Yin , Chenxi Zhou , Ming Wu , Yueyang Deng , Zhanwei Zhou , Minjie Sun . Injectable hydrogel-based tumor vaccine with fibrotic tumor immune microenvironment remodeling to prevent breast cancer postoperative recurrence and metastases. Chinese Chemical Letters, 2025, 36(5): 110067-. doi: 10.1016/j.cclet.2024.110067
17. [17]
  Yang Liu , Yan Liu , Kaiyin Yang , Zhiruo Zhang , Wenbo Zhang , Bingyou Yang , Hua Li , Lixia Chen . A selective HK2 degrader suppresses SW480 cancer cell growth by degrading HK2. Chinese Chemical Letters, 2024, 35(8): 109264-. doi: 10.1016/j.cclet.2023.109264
18. [18]
  Jia-Qi Feng , Xiang Tian , Rui-Ge Cao , Yong-Xiu Li , Wen-Long Liu , Rong Huang , Si-Yong Qin , Ai-Qing Zhang , Yin-Jia Cheng . An AIE-based theranostic nanoplatform for enhanced colorectal cancer therapy: Real-time tumor-tracking and chemical-enhanced photodynamic therapy. Chinese Chemical Letters, 2024, 35(12): 109657-. doi: 10.1016/j.cclet.2024.109657
19. [19]
  Huijiao Fu , Peiqin Liang , Qianwen Chen , Yan Wang , Guang Li , Xuzi Cai , Shengtao Wang , Kun Chen , Shengying Shi , Zhiqiang Yu , Xuefeng Wang . COX-2 blocking therapy in cisplatin chemosensitization of ovarian cancer: An allicin-based nanomedicine approach. Chinese Chemical Letters, 2024, 35(8): 109241-. doi: 10.1016/j.cclet.2023.109241
20. [20]
  Xinyue Han , Yunhan Yang , Jiayin Lu , Yuxiang Lin , Dongxue Zhang , Ling Lin , Liang Qiao . Efficient serum lipids profiling by TiO₂-dopamin-assisted MALDI-TOF MS for breast cancer detection. Chinese Chemical Letters, 2025, 36(5): 110183-. doi: 10.1016/j.cclet.2024.110183

Get Citation

PDF

XML

Metrics

PDF Downloads(8)
Abstract views(1333)
HTML views(122)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142