Oridonin-induced ferroptosis and apoptosis: a dual approach to suppress the growth of osteosarcoma cell DOI Creative Commons
Feifan Zhang,

Yang Hao,

Ning Yang

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 12, 2023

Abstract Background Osteosarcoma (OS) is one of the most common aggressive bone malignancy tumors in adolescents. With no significant advances treatment OS recent ten years, discovering new and effective anti-OS drugs became our top priority. Oridonin has been proved to mediate anti-tumor impact on cells, although it’s mechanism action not fully understood. Methods Here, we investigated inhibitory effect oridonin cells its underlying mechanisms. In 143B U2OS oridonin’s pro-apoptosis pro-ferroptosis effects cell death, proliferation, migration, iron accumulation, mitochondrial membrane potential lipid peroxidation production were observed. Western blot (WB) real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) used detect expression levels apoptosis ferroptosis-relative proteins genes. Iron assay Kit was evaluate relative Fe 2+ content. The detection kit ROS production. changes malignant phenotype examined after treating with ferroptosis inhibitor ferrostatin-1 (Fer-1). Results potently inhibited viability metastasis. Simultaneously, suppressed expressions BAX, cl-caspase3, SLC7A11, GPX4 FTH1 mRNA, while promoting Bcl-2 ACSL4 143 cells. Furthermore, found that also boosted accumulation reactive oxygen species (ROS), encouraged buildup , decreased but this can be reversed by Fer-1. Conclusion trigger collaboratively making it a promising agent for therapy.

Language: Английский

Oridonin-induced ferroptosis and apoptosis: a dual approach to suppress the growth of osteosarcoma cells DOI Creative Commons
Feifan Zhang,

Yang Hao,

Ning Yang

et al.

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 12, 2024

Abstract Background Osteosarcoma (OS) is one of the most common aggressive bone malignancy tumors in adolescents. With application new chemotherapy regimens, finding and effective anti-OS drugs to coordinate program implementation urgent for patients OS. Oridonin had been proved mediate anti-tumor effect on OS cells, but its mechanism has not fully elucidated. Methods The effects oridonin viability, clonal formation migration 143B U2OS cells were detected by CCK-8, colony assays wound-healing test. Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis was used explore Western blot (WB), real-time quantitative PCR (qRT-PCR) detect expression levels apoptosis ferroptosis-relative proteins genes. Annexin V-FITC detection kit flow cytometry examination level apoptosis. Iron assay evaluate relative Fe 2+ content. mitochondrial membrane potential lipid peroxidation production determined ROS kit. Results could effectively inhibit survival, metastasis cells. KEGG results indicated that associated with malignant phenotypic signaling pathways proliferation, migration, drug resistance capable inhibiting expressions BAX, cl-caspase3, SLC7A11, GPX4 FTH1 mRNA, while promoting Bcl-2 ACSL4 Additionally, we found promote accumulation reactive oxygen species (ROS) as well reduce potential, these be significantly reversed ferroptosis inhibitor ferrostatin-1 (Fer-1). Conclusion can trigger collaboratively making it a promising agent therapy.

Language: Английский

Citations

11
SGLT2 inhibitor promotes mitochondrial dysfunction and ER-phagy in colorectal cancer cells DOI Creative Commons

Camilla Anastasio,

Isabella Donisi,

Vitale Del Vecchio

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: May 29, 2024

Abstract Background Sodium-glucose transporter 2 (SGLT2) inhibitors (iSGLT2) are approved medications for type diabetes. Recent studies indicate that iSGLT2 inhibit the growth of some cancer cells. However, mechanism(s) remains to be fully elucidated. Methods The SGLT2 levels were determined in normal colon CCD 841 CoN and, HCT 116, HT-29, SW480 and LoVo colorectal (CRC) cell lines by quantitative real-time PCR western blot. effect canagliflozin on proliferation was examined using CCK-8, as its role CRC cells metabolism tumorigenesis has been evaluated XF HS Seahorse Bioanalyzer flow cytometric analyses. Transient gene silencing experiments analysis protein–protein interaction network conducted evaluate molecular targets Results Data showed treatment with (50 µM) 72 h induced cycle arrest ( p < 0.001), impaired glucose energetic promoted apoptotic death ER stress flowing into autophagy 0.001) 116 HT-29 These cellular events accompanied sirtuin 3 (SIRT3) upregulation 0.01), also supported SIRT3 transient resulting attenuation effects metabolic/energetic alterations induction programmed death. identification validation dipeptidyl peptidase 4 (DPP4) potential common target assessed. Conclusions results deepened knowledge contribution limiting unveiling SGLT2/SIRT3 axis cytotoxic mechanisms. Graphical

Language: Английский

Citations

9
Programmed cell death in hepatocellular carcinoma: mechanisms and therapeutic prospects DOI Creative Commons

Xiang’an Wu,

Jingying Cao,

Xueshuai Wan

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 8, 2024

Hepatocellular Carcinoma (HCC), the most common primary liver cancer, ranks as third cause of cancer-related deaths globally. A deeper understanding cell death mechanisms in HCC is essential for developing more effective treatment strategies. This review explores programmed (PCD) pathways involved HCC, including apoptosis, necroptosis, pyroptosis, ferroptosis, and immunogenic (ICD). These trigger specific cascades that influence development progression HCC. Although multiple PCD are shared cellular factors suggest a possible interplay between different forms death. However, exact roles which pathway plays major role remain unclear. also highlights how disruptions related to drug resistance cancer therapy, promoting combined approach induction anti-tumor enhance therapeutic efficacy. Further research required unravel complex modalities may lead innovative breakthroughs.

Language: Английский

Citations

9
Interactions between the metabolic reprogramming of liver cancer and tumor microenvironment DOI Creative Commons

Haoqiang Yang,

Jinghui Li, Yuanjie Niu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 14, 2025

Metabolic reprogramming is one of the major biological features malignant tumors, playing a crucial role in initiation and progression cancer. The tumor microenvironment consists various non-cancer cells, such as hepatic stellate cancer-associated fibroblasts (CAFs), immune well extracellular matrix soluble substances. In liver cancer, metabolic not only affects its own growth survival but also interacts with other cells by influencing expression release metabolites cytokines (such lactate, PGE2, arginine). This interaction leads to acidification restricts uptake nutrients resulting competition symbiosis. At same time, neighboring during proliferation differentiation processes impacts immunity. article provides comprehensive overview crosstalk between cancer their microenvironment, deepening our understanding relevant findings pathways. contributes further regulation development evasion mechanisms while providing assistance advancing personalized therapies targeting pathways for anti-cancer treatment.

Language: Английский

Citations

1
Ruthenium(ii)–Arene Complex Triggers Immunogenic Ferroptosis for Reversing Drug Resistance DOI

Mengdi Lv,

Yue Zheng,

Xiangyu Dai

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Chemoresistance remains an arduous challenge in oncology, but ferroptosis shows potential for overcoming it by stimulating the immune system. Herein, a novel high-performance ruthenium(II)-based arene complex [Ru(η

Language: Английский

Citations

4
Impact of SGLT2 Inhibitors on Survival in Gastrointestinal Cancer Patients Undergoing Chemotherapy and/or Radiotherapy: A Real-World Data Retrospective Cohort Study DOI Open Access
Lucas E. Flausino, Alexis Germán Murillo Carrasco, Tatiane Katsue Furuya

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

Abstract Background The role of sodium-glucose co-transporter 2 inhibitor (SGLT2i) drugs in the management diabetes and cardiovascular disease is well-established, but emerging evidence suggests potential effects on cancer outcomes, including gastrointestinal (GI) cancers. We conducted an extensive, sex-oriented, real-world data analysis to investigate whether SGLT2i can enhance GI outcomes when used alongside standard therapies such as chemotherapy radiotherapy. Methods study applied a retrospective cohort design with from TriNetX research database ( https://trinetx.com ), examining patients treated and/or radiotherapy between 2013 2023. intervention consisted Gl who received SGLT2i, while control did not. A 5-year follow-up period was used, baseline characteristics were balanced using 1:1 propensity score matching technique. Cox proportional-hazards logistic regression models assessed mortality morbidity risks cohorts. Results included 6,389 male 3,457 female (ICD-10: C15-C25). use significantly associated improved survival for both (HR 0.568; 95% CI 0.534-0.605) 0.561; 0.513-0.614) undergoing also correlated lower hospitalisation rates (OR 0.684; 0.637-0.734) (OR, 0.590; 0.536-0.650) patients. subtypes demonstrated similar benefits, without significant adverse effects. Conclusions Repurposing SGLT2 inhibitors treatment could potentially improve causing side Further clinical trials are needed confirm these findings establish optimal condition its application treatment.

Language: Английский

Citations

0
Intranuclear TCA and mitochondrial overload: the nascent sprout of tumors metabolism DOI

Weixi Yuan,

Guozhong Lu, Yin Zhao

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217527 - 217527

Published: Feb. 1, 2025

Language: Английский

Citations

0
Advances in sodium-glucose transporter protein 2 inhibitors and tumors DOI Creative Commons
Jiaqi Wang, Wenyong Yang

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

Published: Feb. 11, 2025

Tumor is a major challenge to global health and has received extensive attention worldwide due its high degree of malignancy poor prognosis. Although the clinical application targeted therapy immunotherapy improved status quo tumor treatment, development new therapeutic tools for tumors still necessary. Sodium-glucose transporter protein 2 (SGLT2) inhibitors are type glycemic control drugs, which widely used in practice because their effects on weight reduction protection cardiac renal functions. SGLT2 been found be overexpressed many involved tumorigenesis, progression metastasis, suggesting that SGLT2i wide range applications therapy. The aim this article provide comprehensive understanding research progress different by integrating latest studies encourage further exploration therapies trials. This could pave way more effective management strategies outcomes patients.

Language: Английский

Citations

0
Impact of SGLT2 inhibitors on survival in gastrointestinal cancer patients undergoing chemotherapy and/or radiotherapy: a real-world data retrospective cohort study DOI Creative Commons
Lucas E. Flausino, Alexis Germán Murillo Carrasco, Tatiane Katsue Furuya

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 25, 2025

The role of sodium-glucose co-transporter 2 inhibitor (SGLT2i) drugs in the management diabetes and cardiovascular disease is well-established, but emerging evidence suggests potential effects on cancer outcomes, including gastrointestinal (GI) cancers. We conducted an extensive, sex-oriented, real-world data analysis to investigate whether SGLT2i can enhance GI outcomes when used alongside standard therapies such as chemotherapy radiotherapy. study applied a retrospective cohort design with from TriNetX research database ( https://trinetx.com ), examining patients treated and/or radiotherapy between 2013 2023. intervention consisted Gl who received SGLT2i, while control did not. A 5-year follow-up period was used, baseline characteristics were balanced using 1:1 propensity score matching technique. Cox proportional-hazards logistic regression models assessed mortality morbidity risks cohorts. included 6,389 male 3,457 female (ICD-10: C15-C25). use significantly associated improved survival for both (HR 0.568; 95% CI 0.534–0.605) 0.561; 0.513–0.614) undergoing also correlated lower hospitalisation rates (OR 0.684; 0.637–0.734) (OR, 0.590; 0.536–0.650) patients. subtypes demonstrated similar benefits, without significant adverse effects. Repurposing SGLT2 inhibitors treatment could potentially improve causing side Further clinical trials are needed confirm these findings establish optimal condition its application treatment.

Language: Английский

Citations

0
Glutamine’s double-edged sword: fueling tumor growth and offering therapeutic hope DOI Creative Commons

Liguang Fang,

Dandan Gao, Zhe Jiang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 10, 2025

Tumor metabolic reprogramming is a highly complex process that enables tumor survival in the presence of limited nutrients, involving multiple signaling pathways, non-coding RNAs (ncRNAs), and transcription factors. Lately, glutamine has been found to enhance growth, spread, drug resistance cancer cells, while also fostering an immunosuppressive microenvironment aids development. However, some tumors, such as pancreatic melanoma, additional can inhibit proliferation this mechanism closely related regulation immune microenvironment. Therefore, further exploration metabolism tumors essential for understanding pathogenesis developing new metabolically targeted therapies. We systematically review latest research on its role system regulation. Additionally, we clinical progress therapies their application combination with current anti-tumor treatments. Ultimately, address challenges prospects involved anti-cancer strategies aimed at metabolism.

Language: Английский

Citations

0