OncoTargets and Therapy (Jul 2018)

Endoplasmic reticulum stress-mediated autophagy contributes to 5-ethylamino-9-diethylaminobenzo[a]phenoselenazinium-mediated photodynamic therapy via the PERK–eIF2α pathway

  • Chen J,
  • Huang JH,
  • Wang Z,
  • Song X,
  • Chen Z,
  • Zeng Q,
  • Zhou X,
  • Zuo Z,
  • Zhao S,
  • Chen X,
  • Kang J

Journal volume & issue
Vol. Volume 11
pp. 4315 – 4325

Abstract

Read online

Jing Chen,1,* Jin-Hua Huang,1,* Zhen Wang,1,* Xiangzhi Song,2,* Zeyi Chen,1,* Qinghai Zeng,1,* Xiping Zhou,1,* Zhihong Zuo,1,* Shuang Zhao,3,* Xiang Chen,3,* Jian Kang1,* 1Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China *All authors contributed equally to this work Introduction: 5-ethylamino-9-diethylaminobenzo[a]phenoselenazinium (EtNBSe) is a novel synthetic bipolar photosensitizer with many promising applications. This study investigated the impact of EtNBSe-mediated photodynamic therapy (EtNBSe-PDT) on the autophagy and endoplasmic reticulum (ER) stress of squamous carcinoma cells (A-431 cells), as well as the related molecular mechanisms. Methods: The potency of EtNBSe-PDT against squamous cell carcinoma was evaluated in BALB/c nude mice. Cell viability was evaluated using MTT. Western blotting and immunofluorescence were used to determine the expression levels of ER stress- and autophagy-related proteins. Results: Both morphological and microscopic findings showed that the tumor on the xenograft mice exhibited an apparent reduction in volume and was replaced with fibrosis 20 days after EtNBSe-PDT. Additionally, in an in vitro study using A-431 cells, EtNBSe-PDT was found to inhibit A-431 cell survival in an EtNBSe concentration- and light dose- dependent manner, and to induce ER stress via the PERK-eIF2α signaling pathway. Additionally, EtNBSe-PDT could also induce autophagy of A-431 cells. Furthermore, the ER stress inhibitor 4-PBA and the eIF2α inhibitor salubrinal were found to inhibit the autophagy induced by EtNBSe-PDT. Conclusion: This study demonstrated that the PERK-eIF2α signaling pathway was involved in the ER stress induced by EtNBSe-PDT. Meanwhile, the ER stress via the PERK-eIF2α pathway promoted the occurrence of autophagy in A-431 cells. Keywords: photodynamic therapy, endoplasmic reticulum stress, squamous cell carcinoma, autophagy

Keywords