Open Access

PRIMA‑1met induces autophagy in colorectal cancer cells through upregulation of the mTOR/AMPK‑ULK1‑Vps34 signaling cascade

  • Authors:
    • Xiao-Lan Li
    • Jianbiao Zhou
    • Chen-Jing Xia
    • Han Min
    • Zhong-Kai Lu
    • Zhi-Rong Chen
  • View Affiliations

  • Published online on: March 31, 2021     https://doi.org/10.3892/or.2021.8037
  • Article Number: 86
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

p53‑reactivation and induction of massive apoptosis‑1, APR‑017 methylated (PRIMA‑1met; APR246) targets mutant p53 to restore its wild‑type structure and function. It was previously demonstrated that PRIMA‑1met effectively inhibited the growth of colorectal cancer (CRC) cells in a p53‑independent manner, and distinctly induced apoptosis by upregulating Noxa in p53‑mutant cell lines. The present study including experiments of western blotting, acridine orange staining and transmission electron microscopy revealed that PRIMA‑1met induced autophagy in CRC cells independently of p53 status. Importantly, PRIMA‑1met not only promoted autophagic vesicle (AV) formation and AV‑lysosome fusion, but also increased lysosomal degradation. Furthermore, Cell Counting Kit‑8 assay, colony formation assay and small interfering RNA transfection were performed to investigate the underling mechanisms. The study indicated that activation of the mTOR/AMPK‑ULK1‑Vps34 autophagic signaling cascade was key for PRIMA‑1met‑induced autophagy. Additionally, autophagy served a crucial role in the inhibitory effect of PRIMA‑1met in cells harboring wild‑type p53, which was closely associated with the increased expression of Noxa. Taken together, the results determined the effect of PRIMA‑1met on autophagy, and further revealed mechanistic insights into different CRC cell lines. It was concluded that PRIMA‑1met‑based therapy may be an effective strategy for CRC treatment.
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May-2021
Volume 45 Issue 5

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

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Copy and paste a formatted citation
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Spandidos Publications style
Li X, Zhou J, Xia C, Min H, Lu Z and Chen Z: PRIMA‑1<sup>met</sup> induces autophagy in colorectal cancer cells through upregulation of the mTOR/AMPK‑ULK1‑Vps34 signaling cascade. Oncol Rep 45: 86, 2021
APA
Li, X., Zhou, J., Xia, C., Min, H., Lu, Z., & Chen, Z. (2021). PRIMA‑1<sup>met</sup> induces autophagy in colorectal cancer cells through upregulation of the mTOR/AMPK‑ULK1‑Vps34 signaling cascade. Oncology Reports, 45, 86. https://doi.org/10.3892/or.2021.8037
MLA
Li, X., Zhou, J., Xia, C., Min, H., Lu, Z., Chen, Z."PRIMA‑1<sup>met</sup> induces autophagy in colorectal cancer cells through upregulation of the mTOR/AMPK‑ULK1‑Vps34 signaling cascade". Oncology Reports 45.5 (2021): 86.
Chicago
Li, X., Zhou, J., Xia, C., Min, H., Lu, Z., Chen, Z."PRIMA‑1<sup>met</sup> induces autophagy in colorectal cancer cells through upregulation of the mTOR/AMPK‑ULK1‑Vps34 signaling cascade". Oncology Reports 45, no. 5 (2021): 86. https://doi.org/10.3892/or.2021.8037