PRIMA‑1<sup>met</sup> induces autophagy in colorectal cancer cells through upregulation of the mTOR/AMPK‑ULK1‑Vps34 signaling cascade Corrigendum in /10.3892/or.2024.8703

Li,Xiao-Lan; Zhou,Jianbiao; Xia,Chen-Jing; Min,Han; Lu,Zhong-Kai; Chen,Zhi-Rong

doi:10.3892/or.2021.8037

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

Corrigendum in: /10.3892/or.2024.8703

Authors:
- Xiao-Lan Li
- Jianbiao Zhou
- Chen-Jing Xia
- Han Min
- Zhong-Kai Lu
- Zhi-Rong Chen
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Affiliations: Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215001, P.R. China, Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore 117599, Republic of Singapore, Department of Gastroenterology, Traditional Chinese Medicine Hospital of Kunshan, Suzhou, Jiangsu 215300, P.R. China
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‑1^met; APR246) targets mutant p53 to restore its wild‑type structure and function. It was previously demonstrated that PRIMA‑1^met 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‑1^met induced autophagy in CRC cells independently of p53 status. Importantly, PRIMA‑1^met 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‑1^met‑induced autophagy. Additionally, autophagy served a crucial role in the inhibitory effect of PRIMA‑1^met 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‑1^met on autophagy, and further revealed mechanistic insights into different CRC cell lines. It was concluded that PRIMA‑1^met‑based therapy may be an effective strategy for CRC treatment.

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