Procaine induces cell cycle arrest, apoptosis and autophagy through the inhibition of the PI3K/AKT and ERK pathways in human tongue squamous cell carcinoma

Hao,Miao; Zhang,Chu; Shi,Naixu; Yuan,Lin; Zhang,Tianfu; Wang,Xiaofeng

doi:10.3892/ol.2024.14541

Procaine induces cell cycle arrest, apoptosis and autophagy through the inhibition of the PI3K/AKT and ERK pathways in human tongue squamous cell carcinoma

Authors:
- Miao Hao
- Chu Zhang
- Naixu Shi
- Lin Yuan
- Tianfu Zhang
- Xiaofeng Wang
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Affiliations: Scientific Research Center, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Stomatology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
Published online on: June 28, 2024 https://doi.org/10.3892/ol.2024.14541
Article Number: 408
Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Procaine (PCA), a local anesthetic commonly used in stomatology, exhibits antitumor activity in some human malignancies. However, the precise mechanism underlying PCA activity remains unknown, and its antitumor effect in human tongue squamous carcinoma cells has not been reported. Flow cytometry and western blotting were used to assess the effects of PCA on mitochondrial membrane potential (ΔΨm), intracellular reactive oxygen species (ROS) production, cell cycle and apoptosis. The results suggested that PCA inhibits CAL27 and SCC‑15 cell proliferation, and clone formation in a dose‑dependent manner. CAL27 cells were more sensitive to PCA than SCC‑15 cells. PCA also significantly inhibited cell migration, induced mitochondrial damage, reduced ΔΨm and increased intracellular ROS production. PCA causes G2/M cycle arrest and induces apoptosis. The possible mechanism for the inhibition of human tongue squamous carcinoma cell proliferation is through the regulation of ERK phosphorylation and PI3K/AKT‑mediated signaling pathways. The results further suggested that autophagy occurs during PCA‑induced apoptosis in CAL27 cells, and the addition of the autophagy inhibitor hydroxychloroquine sulfate further enhanced the sensitivity of PCA to inhibit cell proliferation, indicating that autophagy plays an important role in protecting cancer cells from apoptosis. PCA shows potential as an anticancer drug and its combination with autophagy inhibitors enhances its sensitivity.

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