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

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Abstract

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.

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Acknowledgements

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).

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Authors and Affiliations

  1. Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, No. 70, Lianhai Road, Gushan District, Kaohsiung, 80424, Taiwan, Republic of China

    Shu-Yu Cheng & Zhi-Hong Wen

  2. Doctoral Degree Program in Marine Biotechnology, Academia Sinica, No. 128, Section 2, Academia Rd, Nangang District, Taipei City, 11529, Taiwan, Republic of China

    Shu-Yu Cheng

  3. Marine Biomedical Laboratory & Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lianhai Road, Gushan District, Kaohsiung, 80424, Taiwan, Republic of China

    Shu-Yu Cheng, Hsiao-Mei Kuo & Zhi-Hong Wen

  4. Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, No. 553, Junxiao Rd., Zuoying Dist., Kaohsiung, 80424, Taiwan, Republic of China

    Nan-Fu Chen

  5. Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Chenggong Road, Neihu District, Taipei City, 114, Taiwan, Republic of China

    Nan-Fu Chen

  6. Center for Neuroscience, National Sun Yat-Sen University, No. 70, Lianhai Road, Gushan District, Kaohsiung, 80424, Taiwan, Republic of China

    Hsiao-Mei Kuo

  7. Department of Pediatrics, E-DA Hospital, School of Medicine, College of Medicine, I-SHOU University, No. 1, Section 1, Xuecheng Road, Dashu District, Kaohsiung, 84001, Taiwan, Republic of China

    San-Nan Yang

  8. Department of Anesthesiology, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Beitou District, Taipei City, 112, Taiwan, Republic of China

    Chun-Sung Sung

  9. School of Medicine, National Yang-Ming University, No. 155, Section 2, Linong St., Beitou District, Taipei City, 112, Taiwan, Republic of China

    Chun-Sung Sung

  10. Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lianhai Road, Gushan District, Kaohsiung, 80424, Taiwan, Republic of China

    Hsiao-Mei Kuo, Ping-Jyun Sung, Zhi-Hong Wen & Wu-Fu Chen

  11. Graduate Institute of Marine Biology, National Dong Hwa University, No. 2, Houwan Road, Checheng Township, Pingtung County, 944, Taiwan, Republic of China

    Ping-Jyun Sung

  12. National Museum of Marine Biology and Aquarium, No. 2, Houwan Road, Checheng Township, Pingtung County, 944, Taiwan, Republic of China

    Ping-Jyun Sung

  13. Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Road, Niaosong District, Kaohsiung, 833, Taiwan, Republic of China

    Wu-Fu Chen

  14. Department of Neurosurgery, Xiamen Chang Gung Hospital, 123 Xiafei Rd, Haicang Qu, Xiamen Shi, Fujian Province, China

    Wu-Fu Chen

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  1. Shu-Yu Cheng
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Cheng, SY., Chen, NF., Kuo, HM. et al. Prodigiosin stimulates endoplasmic reticulum stress and induces autophagic cell death in glioblastoma cells. Apoptosis 23, 314–328 (2018). https://doi.org/10.1007/s10495-018-1456-9

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  • DOI: https://doi.org/10.1007/s10495-018-1456-9

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