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p53‑reactivation and induction of massive apoptosis‑1, APR‑017 methylated (PRIMA‑1 me ; APR246) targets mutant p53 to restore its wild‑type structure and function. It was previously demonstrated that PRIMA‑1 me 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 me induced autophagy in CRC cells independently of p53 status. Importantly, PRIMA‑1 me 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 me ‑induced autophagy. Additionally, autophagy served a crucial role in the inhibitory effect of PRIMA‑1 me 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 me on autophagy, and further revealed mechanistic insights into different CRC cell lines. It was concluded that PRIMA‑1 me ‑based therapy may be an effective strategy for CRC treatment.

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

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