1. Correction: Liu, Y.-S.; et al. Inhibition of Protein Phosphatase 1 Stimulates Noncanonical ER Stress eIF2α Activation to Enhance Fisetin-Induced Chemosensitivity in HDAC Inhibitor-Resistant Hepatocellular Carcinoma Cells. Cancers 2019, 11, 918
- Author
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Chuan-Chou Tu, Ming-Cheng Chen, Chih Yang Huang, Hsi-Hsien Hsu, Po-Hsiang Liao, Yu-Chun Chang, Yu-Lan Yeh, Vijaya Padma Viswanadha, Wei Wen Kuo, and Yi-Sheng Liu
- Subjects
0301 basic medicine ,Cancer Research ,Correction ,Protein phosphatase 1 ,medicine.disease ,Blot ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research ,Unfolded protein response ,medicine ,HDAC inhibitor ,Fisetin - Abstract
Hepatocellular carcinoma (HCC) is a common fatal type of malignant tumor that has highly metastatic and recurrent properties. Fisetin is a natural flavonoid found in various vegetables and fruits which exhibits anti-cancer and anti-inflammatory properties, as well as other effects. Thus, we hypothesized that fisetin can act as an adjuvant therapy in cancer or drug-resistant cancer cells, and further investigated the molecular mechanisms underlying the development of drug-resistance in HCC cells. We found that fisetin effectively inhibited the cell viability of not only parental cells but also histone deacetylase inhibitors-resistant (HDACis-R) cells and enhanced the chemosensitivity of HCC cells. Interestingly, fisetin did not induce cell apoptosis through the activation of the endoplasmic reticulum (ER) stress sensor of protein kinase R (PKR)-like endoplasmic reticulum kinase, but rather through the non-canonical pathway of the protein phosphatase 1 (PP1)-mediated suppression of eIF2α phosphorylation. Moreover, fisetin-induced cell apoptosis was reversed by treatment with PP1 activator or eIF2α siRNA in HCC cells. Based on these observations, we suggest that PP1-eIF2α pathways are significantly involved in the effect of fisetin on HCC apoptosis. Thus, fisetin may act as a novel anticancer drug and new chemotherapy adjuvant which can improve the efficacy of chemotherapeutic agents and diminish their side-effects.
- Published
- 2020