Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and major cause of cancer death in the world. Ferroptosis is a recently identified type of regulated cell death. Increasing evidence has shown that ferroptosis plays an important regulatory role in the occurrence and development of cancer. This study identified TIGAR as a potential regulator of ferroptosis resistance in the development of CRC. We showed that TIGAR expression in CRC tissues is significantly higher than that in adjacent normal tissues. Knockdown of TIGAR significantly caused an increase in erastin-induced ferroptosis in SW620 and HCT116 cells. Notably, knockdown of TIGAR significantly decreased GSH/GSSG ratio, increased lipid peroxidation production, and facilitated the accumulation of lipid peroxidation product malondialdehyde (MDA), and rendered CRC cells more sensitive to erastin induced ferroptosis. Furthermore, TIGAR inhibition repressed SCD1 expression in a redox and AMPK-dependent manner. Thus, these results suggest that TIGAR induces ferroptosis resistance in CRC cells via the ROS/AMPK/SCD1 signaling pathway.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.03.002 | DOI Listing |
Molecules
January 2025
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Epigenetic abnormalities play a critical role in colon carcinogenesis, making them a promising target for therapeutic interventions. In this study, we demonstrated that curcumin reduces colon cancer cell survival and that a decrease in lysine methylation was involved in such an effect. This correlated with the downregulation of methyltransferases EZH2, MLL1, and G9a, in both wild-type p53 (wtp53) HCT116 cells and mutant p53 (mutp53) SW480 cells, as well as SET7/9 specifically in wtp53 HCT116 cells.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Mechanistic Toxicology Branch, Division of Translational Toxicology, National Institutes of Environmental Health Sciences (NIH), Research Triangle Park, Durham, NC 27709, USA.
Acquired resistance to chemotherapeutic drugs is the primary cause of treatment failure in the clinic. While multiple factors contribute to this resistance, increased expression of ABC transporters-such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance proteins-play significant roles in the development of resistance to various chemotherapeutics. We found that Erastin, a ferroptosis inducer, was significantly cytotoxic to NCI/ADR-RES, a P-gp-expressing human ovarian cancer cell line.
View Article and Find Full Text PDFAntibiotics (Basel)
December 2024
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Cancer persists as a significant global health challenge, claiming millions of lives annually despite remarkable strides in therapeutic innovation. Challenges such as drug resistance, toxicity, and suboptimal efficacy underscore the need for novel treatment paradigms. In this context, the repurposing of antibiotics as anti-cancer agents has emerged as an attractive prospect for investigation.
View Article and Find Full Text PDFBiomedicines
January 2025
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
For investigating the host response in associated pneumonia, we analyzed the host genetic sequences obtained from metagenomic next-generation sequencing (mNGS). The samples for mNGS were bronchoalveolar lavage fluid (BALF) collected from the lungs of patients infected with and from patients without bacterial infections. BALF samples from patients with pneumonia were collected from the lungs of patients infected with with New Delhi metallo-β-lactamase (NDM, before treatment), A.
View Article and Find Full Text PDFAntioxidants (Basel)
December 2024
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan.
Hypoxia/reoxygenation (HR) often occurs under cardiac pathological conditions, and HR-induced oxidative stress usually leads to cardiomyocyte damage. Carvedilol, a non-selective β-blocker, is used clinically to treat cardiac ischemia diseases. Moreover, Carvedilol has also been reported to have an antioxidant ability by reducing lipid peroxidation.
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