Induction of apoptosis by pyrazolo[3,4-d]pyridazine derivative in lung cancer cells via disruption of Bcl-2/Bax expression balance

Mohamed, Mervat S.; Abdelhamid, Abdou O.; Almutairi, Fahad M.; Ali, Ayat G.; Bishr, Mai K.

doi:10.1016/j.bmc.2017.12.026

Cited by 32 publications

(13 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Loss of ∆Ψm may result in cytochrome C release into the cytoplasm and then induce caspase‐3 activation–mediated apoptosis 50 . The balance between pro‐apoptosis protein Bax and anti‐apoptosis protein Bcl‐2 determines apoptosis 51 . According to our results, sepsis‐induced myocardial apoptosis was significantly repressed by inhibition of circTLK1 or PARP1.…”

Section: Discussionmentioning

confidence: 62%

CircTLK1 modulates sepsis‐induced cardiomyocyte apoptosis via enhancing PARP1/HMGB1 axis–mediated mitochondrial DNA damage by sponging miR‐17‐5p

Qiu

Qin

et al. 2021

J Cellular Molecular Medi

View full text Add to dashboard Cite

Introduction Septic cardiomyopathy is a common complication of sepsis with high morbidity and mortality, but lacks specific therapy. This study aimed to reveal the role of circTLK1 and its potential mechanisms in septic cardiomyopathy. Materials and Methods The in vitro and in vivo models of septic cardiomyopathy were established. Cell viability and apoptosis were detected by CCK8, TUNEL and flow cytometry, respectively. LDH, CK, SOD, MDA, ATP, 8‐OHdG, NAD+/NADH ratio, ROS level, mitochondrial membrane potential and cytochrome C distribution were evaluated using commercial kits. qRT‐PCR and western blotting were performed to detect RNA and protein levels. Mitochondrial DNA (mtDNA) copy number and transcription were assessed by quantitative PCR. Dual‐luciferase assay, RNA immunoprecipitation and co‐immunoprecipitation were performed to verify the interaction between circTLK1/PARP1 and miR‐17‐5p. Results CircTLK1, PARP1 and HMGB1 were up‐regulated in the in vitro and in vivo models of septic cardiomyopathy. CircTLK1 inhibition restrained LPS‐induced up‐regulation of PARP1 and HMGB1. Moreover, circTLK1 knockdown repressed sepsis‐induced mtDNA oxidative damage, mitochondrial dysfunction and consequent cardiomyocyte apoptosis by inhibiting PARP1/HMGB1 axis in vitro and in vivo. In addition, circTLK1 enhanced PARP1 expression via sponging miR‐17‐5p. Inhibition of miR‐17‐5p abolished the protective effects of circTLK1 silencing on oxidative mtDNA damage and cardiomyocyte apoptosis. Conclusion CircTLK1 sponged miR‐17‐5p to aggravate mtDNA oxidative damage, mitochondrial dysfunction and cardiomyocyte apoptosis via activating PARP1/HMGB1 axis during sepsis, indicating that circTLK1 may be a putative therapeutic target for septic cardiomyopathy.

show abstract

Section: Discussionmentioning

confidence: 62%

CircTLK1 modulates sepsis‐induced cardiomyocyte apoptosis via enhancing PARP1/HMGB1 axis–mediated mitochondrial DNA damage by sponging miR‐17‐5p

Qiu

Qin

et al. 2021

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…29 Cytochrome c in the cytosol participates in the activation of caspase 9, which in turn activates executioner caspase 3 to induce cell apoptosis. 35 –37 Our gene expression analysis suggests that SA induces the mitochondrial pathway of apoptosis in HepG2 cells. SA promotes the gene expressions of p53, Bax and downregulates the expression of Bcl-2, which leads to loss of MMP and results in cytochrome c release from mitochondria and activation of Apaf-1, caspases 9 and 3 leading to apoptosis (Figure 5).…”

Section: Discussionmentioning

confidence: 91%

“…32,33 Further, p53 also induces apoptosis by caspase 9 activation via the release of mitochondrial cytochrome c. The activated caspase 9 in turn activates caspase 3 and is responsible for the degradation of many intracellular proteins resulting in the morphological and biochemical changes of apoptosis. 34 ROS plays a significant role in the mitochondrial membrane damage, thereby triggering a series of mitochondria-associated events including apoptosis. The apoptotic signal or any proapoptotic factors especially ROS directly act on mitochondria or through p53 and reduce the mitochondrial membrane potential (MMP) that is responsible for the release of cytochrome c from mitochondria into the cytosol.…”

Section: Discussionmentioning

confidence: 99%

Syringic acid triggers reactive oxygen species–mediated cytotoxicity in HepG2 cells

2019

View full text Add to dashboard Cite

Hepatocellular carcinoma is the second most common cause of cancer death in the world and its incidence has dramatically increased worldwide in the past two decades. Syringic acid (SA) has been studied for its hepatoprotective, anti-inflammatory, immunomodulatory, free radical scavenging, and antioxidant activities. We aimed to evaluate the cytotoxic effect of SA against human hepatoma HepG2 cell line. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. HepG2 cells were treated with SA at concentration ranges of 25, 50, and 100 µM for 24 h. Reactive oxygen species (ROS) expression was investigated by dichlorofluorescein staining assay. Morphological changes of SA-treated HepG2 cells were evaluated by acridine orange (AO) and ethidium bromide (EB) dual staining. Apoptotic marker gene expressions were evaluated by qPCR. SA treatment caused significant cytotoxicity and liberation of ROS in HepG2 cells. AO and EB staining showed membrane blebbing and distortion in SA-treated cells. Apoptotic markers such as caspases 3 and 9, cytochrome c, Apaf-1, Bax, and p53 gene expressions were significantly increased upon SA treatment indicating the possibility of apoptosis induction in HepG2 cells. This treatment also caused significant downregulation of Bcl-2 gene expression. SA has a cytotoxic effect on human HepG2 cell line, and this might be a promising agent in anticancer research.

show abstract

“…27 The Pi3k–Akt pathway is a general pathway related to cell proliferation, 28,29 and Bcl-2/Bax is mainly responsible for regulating apoptosis. 30 We further explored a series of common signaling pathways, including the previously mentioned pathways, and ultimately found that scutellarein had the most significant effects on the TGF–Smad pathway, the Pi3k–Akt pathway, and the Bcl-2/Bax pathway.…”

Section: Discussionmentioning

confidence: 99%

Scutellarein inhibits BLM-mediated pulmonary fibrosis by affecting fibroblast differentiation, proliferation, and apoptosis

Miao¹,

Pan²,

Mou³

et al. 2020

Therapeutic Advances in Chronic Disease

View full text Add to dashboard Cite

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial pulmonary disease that has a poor prognosis. Scutellarein, which is extracted from the traditional Chinese medicine Erigeron breviscapus, is used to treat a variety of diseases; however, the use of scutellarein for the treatment of pulmonary fibrosis and the related mechanisms of action have not been fully explored. Methods: This study was conducted using a well-established mouse model of pulmonary fibrosis induced by bleomycin (BLM). The antifibrotic effects of scutellarein on histopathologic manifestations and fibrotic marker expression levels were examined. The effects of scutellarein on fibroblast differentiation, proliferation, and apoptosis and on related signaling pathways were next investigated to demonstrate the underlying mechanisms. Results: In the present study, we found that scutellarein alleviated BLM-induced pulmonary fibrosis, as indicated by histopathologic manifestations and the expression levels of fibrotic markers. Further data demonstrated that the ability of fibroblasts to differentiate into myofibroblasts was attenuated in scutellarein-treated mice model. In addition, we obtained in vitro evidence that scutellarein inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-β/Smad signaling, inhibited cellular proliferation by repressing PI3K/Akt signaling, and increased apoptosis of fibroblasts by affecting Bax/Bcl2 signaling. Discussion: In general, scutellarein might exert therapeutic effects on pulmonary fibrosis by altering the differentiation, proliferation, and apoptosis of fibroblasts. Although scutellarein has been demonstrated to be safe in mice, further studies are required to investigate the efficacy of scutellarein in patients with IPF.

show abstract

Induction of apoptosis by pyrazolo[3,4-d]pyridazine derivative in lung cancer cells via disruption of Bcl-2/Bax expression balance

Cited by 32 publications

References 25 publications

CircTLK1 modulates sepsis‐induced cardiomyocyte apoptosis via enhancing PARP1/HMGB1 axis–mediated mitochondrial DNA damage by sponging miR‐17‐5p

CircTLK1 modulates sepsis‐induced cardiomyocyte apoptosis via enhancing PARP1/HMGB1 axis–mediated mitochondrial DNA damage by sponging miR‐17‐5p

Syringic acid triggers reactive oxygen species–mediated cytotoxicity in HepG2 cells

Scutellarein inhibits BLM-mediated pulmonary fibrosis by affecting fibroblast differentiation, proliferation, and apoptosis

Contact Info

Product

Resources

About