ω3-polyunsaturated fatty acids induce cell death through apoptosis and autophagy in glioblastoma cells: In vitro and in vivo

  • Authors:
    • Soyeon Kim
    • Kaipeng Jing
    • Soyeon Shin
    • Soyeon Jeong
    • Seung-Hyeon Han
    • Heyrim Oh
    • Yoon-Seon Yoo
    • Jeongsu Han
    • Young-Joo Jeon
    • Jun-Young Heo
    • Gi-Ryang Kweon
    • Seung-Kiel Park
    • Jong-Il Park
    • Tong Wu
    • Kyu Lim
  • View Affiliations

  • Published online on: November 16, 2017     https://doi.org/10.3892/or.2017.6101
  • Pages:239-246
Metrics: HTML 0 views | PDF 0 views
0

Abstract

Among brain tumors, glioblastoma (GBM) is the most aggressive type and is associated with the lowest patient survival rate. Numerous lines of evidence have established that omega-3-polyunsaturated fatty acids (ω3-PUFAs) have potential for the prevention and therapy of several types of cancers. Docosahexaenoic acid (DHA), an ω3-PUFA, was reported to inhibit growth and induce apoptotic and autophagic cell death in several cancer cell lines; however, its effects on GBM cells are still unknown. in the present study, we examined the cytotoxic effect of DHA on the GBM cell lines, D54MG, U87MG, U251MG and GL261. Treatment of GBM cells with DHA induced PARP cleavage, increased the population of sub-G1 cells, and increased the number of TUNEL-positive cells, which are all indicative of apoptosis. Furthermore, treatment of GBM cells with DHA resulted in a significant increase in autophagic activity, as revealed by increased LC3-II levels, GFP-LC3 puncta, and autophagic flux activation, accompanied by activation of 5'-AMP-activated protein kinase (AMPK) and decreases in phosphorylated Akt (p-AktSer473) levels and mTOR activity. In vivo, endogenous expression of Caenorhabditis elegans ω3-desaturase, which converts ω6-PUFAs to ω3-PUFAs, in fat-1 transgenic mice yielded a significant decrease in tumor volume following subcutaneous injection of mouse glioma cells (GL261), when compared with wild-type mice. TUNEL-positive cell numbers and LC3-II levels were elevated in tumor tissue from the fat-1 transgenic mice compared with tumor tissue from the wild-type mice. In addition, p-Akt levels were decreased and p-AMPK levels were increased in tumor tissue from the fat-1 transgenic mice. These results indicate that ω3-PUFAs induce cell death through apoptosis and autophagy in GBM cells; thus, it may be possible to use ω3-PUFAs as chemopreventive and therapeutic agents for GBM.

Related Articles

Journal Cover

January 2018
Volume 39 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

2016 Impact Factor: 2.662
Ranked #31/217 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Kim, S., Jing, K., Shin, S., Jeong, S., Han, S., Oh, H. ... Lim, K. (2018). ω3-polyunsaturated fatty acids induce cell death through apoptosis and autophagy in glioblastoma cells: In vitro and in vivo. Oncology Reports, 39, 239-246. https://doi.org/10.3892/or.2017.6101
MLA
Kim, S., Jing, K., Shin, S., Jeong, S., Han, S., Oh, H., Yoo, Y., Han, J., Jeon, Y., Heo, J., Kweon, G., Park, S., Park, J., Wu, T., Lim, K."ω3-polyunsaturated fatty acids induce cell death through apoptosis and autophagy in glioblastoma cells: In vitro and in vivo". Oncology Reports 39.1 (2018): 239-246.
Chicago
Kim, S., Jing, K., Shin, S., Jeong, S., Han, S., Oh, H., Yoo, Y., Han, J., Jeon, Y., Heo, J., Kweon, G., Park, S., Park, J., Wu, T., Lim, K."ω3-polyunsaturated fatty acids induce cell death through apoptosis and autophagy in glioblastoma cells: In vitro and in vivo". Oncology Reports 39, no. 1 (2018): 239-246. https://doi.org/10.3892/or.2017.6101