Objective: To investigate the effect of sanguinarine (SAN) on proliferation and ferroptosis of colorectal cancer cells.
Methods: SW620 and HCT-116 cells treated with different concentrations of SAN were examined for cell viability changes using CCK8 assay to determine the IC of SAN in the two cells. The inhibitory effects of SAN on proliferation, invasion and migration of the cells were evaluated using colony-forming assay and Transwell assays. ROS production in the treated cells was analyzed with flow cytometry, and lipid peroxide production was assessed by detecting malondialdehyde (MDA) level. Glutathione (GSH) levels in the cells were detected, and Western blotting was used to detect the expressions of ferroptosis-related proteins STUB1 and GPX4.
Results: SAN significantly inhibited the proliferation, invasion and migration of SW620 and HCT-116 cells. SAN treatment significantly promoted ROS production, increased intracellular MDA level, and lowered GSH level in the two cells (<0.05). Western blotting showed that SAN significantly upregulated the expression of STUB1 and down-regulated the expression of its downstream protein GPX4 (<0.05).
Conclusion: SAN induces ferroptosis in colorectal cancer cells by regulating STUB1/GPX4, which may serve as a new therapeutic target for colorectal cancer.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2024.08.12 | DOI Listing |
Mol Cell Probes
January 2025
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Electronic address:
Ferroptosis is a regulated cell death mechanism distinct from apoptosis, autophagy, and necroptosis, marked by iron accumulation and lipid peroxidation. Since its identification in 2012, it has developed into a potential therapeutic target, especially concerning GI disorders like PC, HCC, GC, and CRC. This interest arises from the distinctive role of ferroptosis in the progression of diseases, presenting a new avenue for treatment where existing therapies fall short.
View Article and Find Full Text PDFJ Cell Biochem
January 2025
Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China.
tRNA-derived fragments (tRFs) are a newly recognized class of small noncoding RNAs (sncRNAs) that play significant roles in various diseases. The Wnt pathway plays a key role in various physiological processes such as embryonic development, tissue renewal and regeneration. In the regulation of Wnt/β-catenin, Forkhead box k1(FOXK1), Frizzled class receptor 3 (FZD3), and Wnt5b can be targeted and inhibited by three tRFs: tRF3008A targets FOXK1 to inhibit colorectal cancer (CRC), 5'-tiRNAVal targets FZD3 to inhibit breast cancer (BrC), and tRF-22-8BWS7K092 targets Wnt5b to induce ferroptosis in lung cells.
View Article and Find Full Text PDFNat Commun
January 2025
Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
S-palmitoylation is a reversible and widespread post-translational modification, but its role in the regulation of ferroptosis has been poorly understood. Here, we elucidate that GPX4, an essential regulator of ferroptosis, is reversibly palmitoylated on cysteine 66. The acyltransferase ZDHHC20 palmitoylates GPX4 and increases its protein stability.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Department of General Surgery, Tianjin Fifth Central Hospital, No. 41 Zhejiang Road, Binhai New Area, Tianjin, 300450, China.
Gastric cancer (GC), a prevalent malignancy worldwide, encompasses a multitude of biological processes in its progression. Recently, ferroptosis, a novel mode of cell demise, has become a focal point in cancer research. The microenvironment of gastric cancer is composed of diverse cell populations, yet the specific gene expression profiles and their association with ferroptosis are not well understood.
View Article and Find Full Text PDFDig Dis Sci
January 2025
Ningxia Medical University, Xing Qing Block, Shengli Street No.1160, Yin Chuan City, 750004, Ningxia Province, People's Republic of China.
Background: Colon adenocarcinoma (COAD) is a leading cause of cancer-related mortality worldwide. Transient receptor potential vanilloid 4 (TRPV4), a calcium-permeable non-selective cation channel, has been implicated in various cancers, including COAD. This study investigates the role of TRPV4 in colon adenocarcinoma and elucidates its potential mechanism via the ferroptosis pathway.
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