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
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