UM171 suppresses breast cancer progression by inducing KLF2 DOI Creative Commons
Xiaojuan Ran, Anling Hu,

Yi Kuang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 12, 2024

Abstract Purpose: Breast cancer is the most frequent in women with significant death rate. Morbidity associated drug resistance and metastasis. Development of novel drugs unmet need. The aim this study to show potent anti-neoplastic activity UM171 compound on breast cells its mechanism action. Methods: inhibitory effect several (BC) cell lines was examined using MTT colony forming assays. Cell cycle apoptosis assays were utilized determine BC proliferation survival. Wound healing scratch transwell migration used examine culture. Xenograft mouse model 4T1 in vivo. Q-RT-PCR western blotting expression level genes effected by UM171. Lentivirus-mediated shRNA knockdown KLF2 cells. Results: previously identified as a agonist human hematopoietic stem renewal inhibitor leukemia. In study, shown inhibit growth multiple UM171-mediated inhibition induction apoptosis, G2/M arrest, lower capacity reduced motility. xenotransplantation triple negative injected into syngeneic BALB/c mice, strongly inhibited tumor at comparable paclitaxel. increased three PIM (PIM1-3) Moreover, induced suppressor gene KLF2 P21CIP1. Accordingly, lentivirus-mediated significantly attenuated As PIM1-3 act oncogenes are involved progression, these kinases likely impedes combination PAN-PIM LGH447 Conclusion: These results suggested that progression part through activation P21. Combination offer therapy for aggressive forms cancer.

Language: Английский

Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer DOI Creative Commons
Hua Su, Chao Peng, Yang Liu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: March 18, 2024

The global challenge posed by cancer, marked rising incidence and mortality rates, underscores the urgency for innovative therapeutic approaches. PI3K/Akt signaling pathway, frequently amplified in various cancers, is central regulating essential cellular processes. Its dysregulation, often stemming from genetic mutations, significantly contributes to cancer initiation, progression, resistance therapy. Concurrently, ferroptosis, a recently discovered form of regulated cell death characterized iron-dependent processes lipid reactive oxygen species buildup, holds implications diseases, including cancer. Exploring interplay between dysregulated pathway ferroptosis unveils potential insights into molecular mechanisms driving or inhibiting ferroptotic cells. Evidence suggests that may sensitize cells induction, offering promising strategy overcome drug resistance. This review aims provide comprehensive exploration this interplay, shedding light on disrupting enhance as an alternative route inducing improving treatment outcomes.

Language: Английский

Citations

25
Cinnamaldehyde mitigates acute myocardial infarction by regulating ferroptosis through the PI3K-AKT signaling pathway DOI
Ming Yang, Dongming Lin,

Liming He

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114262 - 114262

Published: Feb. 11, 2025

Language: Английский

Citations

2
METTL14 decreases FTH1 mRNA stability via m6A methylation to promote sorafenib-induced ferroptosis of cervical cancer DOI Creative Commons
Lijie Li, Jie Zeng, Sili He

et al.

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: May 13, 2024

Cervical cancer (CC) is a prevalent malignancy among women worldwide. This study was designed to investigate the role of METTL14 in sorafenib-induced ferroptosis CC. expression and m6A methylation were determined CC tissues, followed by analyzes correlating these factors with clinical features. Subsequently, knocked down cell lines, effects on proliferation, mitochondrial morphology assessed using CCK-8, microscopy, markers associated ferroptosis, respectively. The regulatory relationship between FTH1 verified qRT-PCR luciferase reporter assays. functional significance this interaction further investigated both vitro vivo co-transfecting cells overexpression vectors or shRNAs targeting after sorafenib treatment. significantly reduced lower levels poorer patients' prognosis. Notably, increased during knockdown attenuated ferroptotic response induced cells. identified as direct target METTL14, leading mRNA, resulting stability Furthermore, treatment LY294002 partially counteracted promotion METTL14. In xenograft experiments demonstrated that inhibiting anticancer sorafenib, whereas suppression enhanced its efficacy. reduces mRNA through methylation, thereby enhancing which contributes suppressing progression via PI3K/Akt signaling pathway.

Language: Английский

Citations

11
Mechanism of metal ion-induced cell death in gastrointestinal cancer DOI Open Access

Muhua Luan,

Zhaotian Feng,

Wenshuai Zhu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116574 - 116574

Published: April 8, 2024

Gastrointestinal (GI) cancer is one of the most severe types cancer, with a significant impact on human health worldwide. Due to urgent demand for more effective therapeutic strategies against GI cancers, novel research metal ions treating cancers has attracted increasing attention. Currently, accumulating relationship between and therapy, several have been discovered induce cell death. In particular, three modes death, including ferroptosis, cuproptosis, calcicoptosis, become focal points in field cancer. Meanwhile, other also found trigger death through various mechanisms. Accordingly, this review focuses mechanisms ion-induced hoping provide theoretical support further therapies.

Language: Английский

Citations

9
Selective PI3Kδ inhibitor TYM-3-98 suppresses AKT/mTOR/SREBP1-mediated lipogenesis and promotes ferroptosis in KRAS-mutant colorectal cancer DOI Creative Commons
Yanan Zheng, Siyue Lou,

Jun Lu

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(7)

Published: July 3, 2024

Abstract Colorectal cancer (CRC) is one of the most common tumors digestive system worldwide. KRAS mutations limit use anti-EGFR antibodies in combination with chemotherapy for treatment CRC. Therefore, novel targeted therapies are needed to overcome KRAS-induced oncogenesis. Recent evidence suggests that inhibition PI3K led ferroptosis, a nonapoptotic cell death closely related KRAS-mutant cells. Here, we showed selective PI3Kδ inhibitor TYM-3–98 can suppress AKT/mTOR signaling and activate ferroptosis pathway CRC cells concentration-dependent manner. This was evidenced by lipid peroxidation, iron accumulation, depletion GSH. Moreover, overexpression sterol regulatory element-binding protein 1 (SREBP1), downstream transcription factor regulating metabolism, conferred greater resistance induced TYM-3–98. In addition, effect confirmed xenograft mouse model, which demonstrated significant tumor suppression without obvious hepatoxicity or renal toxicity. Taken together, our work induction contributed inhibitor-induced via AKT/mTOR/SREBP1-mediated lipogenesis, thus displaying promising therapeutic treatment.

Language: Английский

Citations

6
Ferroptosis in Cancer Progression DOI Creative Commons
Rongyu Zhang, Jinghong Chen,

Saiyang Wang

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(14), P. 1820 - 1820

Published: July 10, 2023

Ferroptosis is a newly discovered iron-dependent form of regulated cell death driven by phospholipid peroxidation and associated with processes including iron overload, lipid peroxidation, dysfunction cellular antioxidant systems. found to be closely related many diseases, cancer at every stage. Epithelial–mesenchymal transition (EMT) in malignant tumors that originate from epithelia promotes cancer-cell migration, invasion, metastasis disrupting cell–cell matrix junctions, polarity, etc. Recent studies have shown ferroptosis appears share multiple initiators overlapping pathways EMT cancers identify as potential predictor various grades prognoses. Cancer involves steps, local invasion cells, intravasation, survival circulation, arrest distant organ site, extravasation adaptation foreign tissue microenvironments, angiogenesis, the formation “premetastatic niche”. Numerous revealed metastasis. From perspective, has been implicated regulation molecular signaling activated during two events interweave. This review briefly introduces mechanisms discusses how involved progression, EMT,

Language: Английский

Citations

15
Oxyresveratrol as a novel ferroptosis inducer exhibits anticancer activity against breast cancer via the EGFR/PI3K/AKT/GPX4 signalling axis DOI Creative Commons
Lei Xiang,

Qingzhou Li,

Zhiwei Guan

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

Oxyresveratrol (ORes) exhibits significant anticancer activity, particularly against breast cancer. However, its exact mechanism of action (MOA) remains unclear. This study aimed to investigate the pharmacological activity and underlying MOA. The inhibitory effect ORes on cancer cell growth was confirmed, effective concentrations were determined for further experiments. Gene expression profiles (GEPs) collected from MDA-MB-231 cells treated with at varying using HTS2. Bioinformatics tools used predict MOA ORes. Ferroptosis markers (ferrous ions, reactive oxygen species, lipid peroxidation, GPX4 expression) assessed, mitochondrial morphology observed. tumour evaluated in vivo, along analysis ferroptosis tissues. explored L1000, Drug DataBase (DGDB), Western blotting analyses. significantly reduces viability proliferation a concentration-dependent manner, IC50 values 104.8 μM, 150.2 143.6 μM MDA-MB-231, BT-549, 4T1 cells, respectively. GEPs induced by enriched PI3K/AKT signalling pathways. inhibited growth, increased intracellular ferrous ion levels, ferroptosis-related alterations. These effects associated decreased suppression EGFR, phosphorylated PI3K, AKT. enhanced iron deposition, reduced tissues vivo. Notably, treatment inhibitor ferrostatin-1 (Ferr-1) attenuated ORes, confirming pivotal role ORes-mediated inhibition. inhibits inducing through EGFR/PI3K/AKT/GPX4 axis. suggests that holds promise as potential therapeutic agent warrants investigation into clinical applications integration existing regimens.

Language: Английский

Citations

0
Identification of PIF1 as a Ferroptosis-Related Prognostic Biomarker Correlated with Immune Infiltration in Hepatocellular Carcinoma DOI

Feng Liu,

Ping Yin,

Lifang Lu

et al.

Applied Biochemistry and Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Language: Английский

Citations

0
A novel mechanism in regulating drug sensitivity, growth, and apoptosis of bortezomib-resistant multiple myeloma cells: the USP4/KLF2/HMGA2 cascade DOI Creative Commons
Ziyi Liu, Xiaoliang Li,

Y. He

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 1, 2025

Multiple myeloma (MM) is a malignant disorder originating from plasma cells. Bortezomib (BTZ) resistance has become huge obstacle to MM treatment. Herein, we elucidated the action of Kruppel-like factor 2 (KLF2), crucial transcription (TF), on BTZ MM. Two BTZ-resistant cell lines (MM1.S/BTZ and NCI-H929/BTZ) were generated used. KLF2 mRNA was quantified by quantitative PCR, protein expression analyzed immunoblotting. MTT cytotoxicity assay used test sensitivity. Cell growth detected EdU assays. Flow cytometry for apoptosis cycle distribution analyses. The USP4/KLF2 relationship examined Co-IP stability KLF2/HMGA2 interplay confirmed luciferase ChIP Upregulation observed in serum Depletion suppressed enhanced sensitivity MM1.S/BTZ NCI-H929/BTZ Moreover, USP4 increased deubiquitination affected growth, via KLF2. functioned as regulator HMGA2 modulated through HMGA2. Additionally, two lines. Our study demonstrates role USP4/KLF2/HMGA2 cascade regulating cells, providing novel targets improving anti-MM efficacy BTZ.

Language: Английский

Citations

0
Shikonin Derivative Suppresses Colorectal Cancer Cells Growth via Reactive Oxygen Species‐Mediated Mitochondrial Apoptosis and PI3K/AKT Pathway DOI Open Access
Hongwei Han, Zhongling Wen, Minkai Yang

et al.

Chemistry & Biodiversity, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

ABSTRACT Colorectal cancer (CRC) is one of the deadliest cancers globally, ranking as third most prevalent and second lethal malignancy worldwide. The standard treatment for CRC typically involves a combination surgery, radiotherapy, chemotherapy. Despite advancements in treatment, prognosis remains unsatisfactory, primarily due to unclear mechanisms underlying tumorigenesis aggression CRC. aberrant activation PI3K/AKT pathway frequently implicated initiation, progression, metastasis Studies have demonstrated that shikonin (SK) exerts anti‐cancer effects. In this study, we evaluated anti‐tumor activities series semi‐synthesized SK derivatives against cells. Our findings revealed derivative (M12) significantly inhibited proliferation colony formation cells, reduced cell migration, induced apoptosis. Mechanistically, M12 enhanced production reactive oxygen species downregulated mitochondrial membrane potential, ultimately leading Furthermore, exhibited anti‐CRC effects by modulating signaling suppressed tumorigenicity without causing notable adverse mice. Therefore, targeting could be promising appears candidate effective safe

Language: Английский

Citations

0