, Volume 23, Issue 5–6, pp 314–328 | Cite as

Prodigiosin stimulates endoplasmic reticulum stress and induces autophagic cell death in glioblastoma cells

  • Shu-Yu Cheng
  • Nan-Fu Chen
  • Hsiao-Mei Kuo
  • San-Nan Yang
  • Chun-Sung Sung
  • Ping-Jyun Sung
  • Zhi-Hong Wen
  • Wu-Fu Chen


Prodigiosin, a secondary metabolite isolated from marine Vibrio sp., has antimicrobial and anticancer properties. This study investigated the cell death mechanism of prodigiosin in glioblastoma. Glioblastoma multiforme (GBM) is an aggressive primary cancer of the central nervous system. Despite treatment, or standard therapy, the median survival of glioblastoma patients is about 14.6 month. The results of the present study clearly showed that prodigiosin significantly reduced the cell viability and neurosphere formation ability of U87MG and GBM8401 human glioblastoma cell lines. Moreover, prodigiosin with fluorescence signals was detected in the endoplasmic reticulum and found to induce excessive levels of autophagy. These findings were confirmed by observation of LC3 puncta formation and acridine orange staining. Furthermore, prodigiosin caused cell death by activating the JNK pathway and decreasing the AKT/mTOR pathway in glioblastoma cells. Moreover, we found that the autophagy inhibitor 3-methyladenine reversed prodigiosin induced autophagic cell death. These findings of this study suggest that prodigiosin induces autophagic cell death and apoptosis in glioblastoma cells.


Prodigiosin Autophagic cell death Glioblastoma 



This research was supported by Ministry of Science and Technology, Taiwan (105-2320-B-182A-015), National Research Program for Biopharmaceuticals, Taiwan (105-2325-B-110-001), and Chang Gung Memorial Hospital, Taiwan (CMRPG8D0821).

Supplementary material

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Supplementary material 1 (DOCX 958 KB)
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Supplementary material 2 (XLSX 35 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Shu-Yu Cheng
    • 1
    • 2
    • 3
  • Nan-Fu Chen
    • 4
    • 5
  • Hsiao-Mei Kuo
    • 3
    • 6
    • 10
  • San-Nan Yang
    • 7
  • Chun-Sung Sung
    • 8
    • 9
  • Ping-Jyun Sung
    • 10
    • 11
    • 12
  • Zhi-Hong Wen
    • 1
    • 3
    • 10
  • Wu-Fu Chen
    • 10
    • 13
    • 14
  1. 1.Doctoral Degree Program in Marine BiotechnologyNational Sun Yat-Sen UniversityKaohsiungTaiwan, Republic of China
  2. 2.Doctoral Degree Program in Marine BiotechnologyAcademia SinicaTaipei CityTaiwan, Republic of China
  3. 3.Marine Biomedical Laboratory & Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and ResourcesNational Sun Yat-sen UniversityKaohsiungTaiwan, Republic of China
  4. 4.Division of Neurosurgery, Department of SurgeryKaohsiung Armed Forces General HospitalKaohsiungTaiwan, Republic of China
  5. 5.Department of Neurological Surgery, Tri-Service General HospitalNational Defense Medical CenterTaipei CityTaiwan, Republic of China
  6. 6.Center for NeuroscienceNational Sun Yat-Sen UniversityKaohsiungTaiwan, Republic of China
  7. 7.Department of Pediatrics, E-DA Hospital, School of Medicine, College of MedicineI-SHOU UniversityKaohsiungTaiwan, Republic of China
  8. 8.Department of AnesthesiologyTaipei Veterans General HospitalTaipei CityTaiwan, Republic of China
  9. 9.School of MedicineNational Yang-Ming UniversityTaipei CityTaiwan, Republic of China
  10. 10.Department of Marine Biotechnology and ResourcesNational Sun Yat-sen UniversityKaohsiungTaiwan, Republic of China
  11. 11.Graduate Institute of Marine BiologyNational Dong Hwa UniversityChecheng TownshipTaiwan, Republic of China
  12. 12.National Museum of Marine Biology and AquariumChecheng TownshipTaiwan, Republic of China
  13. 13.Department of NeurosurgeryKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiungTaiwan, Republic of China
  14. 14.Department of NeurosurgeryXiamen Chang Gung HospitalXiamen ShiChina

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