scholarly journals Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Linyan Lv ◽  
Yajie Chang ◽  
Yanqing Li ◽  
Haicheng Chen ◽  
Jiahui Yao ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Cell Apoptosis ◽  
Mitochondrial Dynamics ◽  
Reproductive Toxicity ◽  
Mitochondrial Apoptosis ◽  
Mitochondrial Dynamic ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Triptolide is widely used in the clinical treatment of various diseases. Side effects, including reproductive toxicity to male patients, limit its application. However, no detailed mechanisms or potential intervention targets have been reported. In this study, we show that triptolide activated the mitochondrial apoptosis pathway in rat testicular Leydig cells and induced apoptosis both in vivo and in vitro, which may cause hypoleydigism and impair spermatogenesis. Mechanistically, triptolide-induced dynamin-related protein 1 (Drp1) overexpression, which interfered with mitochondrial dynamic stability to activate the mitochondrial apoptosis pathway. Mdivi-1, a selective Drp1 inhibitor, partially reversed the mitochondrial dynamic disturbance and rat testicular Leydig cell apoptosis induced by triptolide. Inhibiting Drp1 over-activation may be a new strategy for mitigating the reproductive toxicity of triptolide.

scholarly journals Myricitrin Protects against Doxorubicin-Induced Cardiotoxicity by Counteracting Oxidative Stress and Inhibiting Mitochondrial Apoptosis via ERK/P53 Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Jing Sun ◽  
Guibo Sun ◽  
Xiaolan Cui ◽  
Xiangbao Meng ◽  
Meng Qin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Damage ◽  
Mitochondrial Apoptosis ◽  
Mechanism Study ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Myocardial Apoptosis ◽  
Underlying Mechanisms

Doxorubicin (Dox) is one of the most effective and widely used anthracycline antineoplastic antibiotics. Unfortunately, the use of Dox is limited by its cumulative and dose-dependent cardiac toxicity. Myricitrin, a natural flavonoid which is isolated from the ground bark ofMyrica rubra, has recently been found to have a strong antioxidative effect. This study aimed to evaluate the possible protective effect of myricitrin against Dox-induced cardiotoxicity and the underlying mechanisms. An in vivo investigation in SD rats demonstrated that myricitrin significantly reduced the Dox-induced myocardial damage, as indicated by the decreases in the cardiac index, amelioration of heart pathological injuries, and decreases in the serum cardiac enzyme levels. In addition, in vitro studies showed that myricitrin effectively reduced the Dox-induced cell toxicity. Further study showed that myricitrin exerted its function by counteracting oxidative stress and increasing the activities of antioxidant enzymes. Moreover, myricitrin suppressed the myocardial apoptosis induced by Dox, as indicated by decreases in the activation of caspase-3 and the numbers of TUNEL-positive cells, maintenance of the mitochondrial membrane potential, and increase in the Bcl-2/Bax ratio. Further mechanism study revealed that myricitrin-induced suppression of myocardial apoptosis relied on the ERK/p53-mediated mitochondrial apoptosis pathway.

scholarly journals Camalexin Induces Apoptosis via the ROS-ER Stress-Mitochondrial Apoptosis Pathway in AML Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Yang Yang ◽  
Gang Wang ◽  
Wenjun Wu ◽  
Shunnan Yao ◽  
Xiaoyan Han ◽  
...  
Keyword(s):  
Er Stress ◽  
Plant Pathogens ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Mitochondrial Apoptosis ◽  
Antitumor Effects ◽  
Sod Activity ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Camalexin is a phytoalexin that accumulates in various cruciferous plants upon exposure to environmental stress and plant pathogens. It was shown that camalexin has potent antitumor properties, but its underlying mechanisms are still elusive. In the present study, we evaluated the effects of camalexin on human leukemic cells and normal polymorph nuclear cells. CCK-8 assay was used to determine cell viability after camalexin treatment. Apoptosis, intracellular reactive oxygen species (ROS) levels, and loss of mitochondrial membrane potential (MMP) were measured by flow cytometry. The activity of SOD, catalase, and ratio of GSH/GSSG were assayed. ER stress and apoptotic signaling pathway was examined by Western blot. Xenograft mice were used to verify the effect of camalexin in vivo. Our results indicated that camalexin inhibited viability of leukemic but not normal polymorph nuclear cells. Furthermore, camalexin induces apoptosis via the mitochondrial pathway in a caspase-dependent manner. We also observed ER stress is located upstream of apoptosis induced by camalexin. Besides, ROS levels, SOD activity, CAT activity, and GSSG levels were significantly enhanced while the GSH level was decreased after treatment of camalexin. In addition, the generation of ROS is critical for the ER stress and apoptosis induced by camalexin. Finally, administration of camalexin suppresses xenograft tumor graft growth without obvious toxicity. Taken together, this study indicates that camalexin exerts antitumor effects against leukemia cells via the ROS-ER stress-mitochondrial apoptosis pathway.

Curcumin Promotes Anti-Tumor Effect of Cisplatin and Protects Against Cisplatin-Induced Kidney Injury in Lung Cancer

2021 ◽  
Author(s):  
Miaoxin Zhao ◽  
Yue Ma ◽  
Xiangka Hu ◽  
Yuqi Sun ◽  
Zuodong Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kidney Injury ◽  
Term Treatment ◽  
Combination Regimen ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
In Vivo Experiments ◽  
Long Term Treatment

Abstract Background: Lung cancer patients will develop strong drug resistance and serious complications, especially severe renal injuries, after long-term treatment of platinum-based drugs. Curcumin (Cur) combined with cisplatin (DDP) has a synergistic and attenuating effect on lung cancer. However, the role of curcumin in protection against DDP kidney injury in lung cancer remains unknown. Methods: We conducted in vitro experiments to evaluate the anti-tumor effect of cur combined with DDP such as MTT, mitochondrial membrane potential (ΔΨm) analysis, and flow cytometry. The serology and histopathology were used to assess kidney injury induced by DDP in vivo experiments. Western blotting analysis was utilized to detect P38 levels in mouse kidneys. Results: A significant synergistic antitumor effect in A549 and LLC-1 cells based on the activation of the mitochondrial apoptosis pathway. Moreover, Cur could reduce the nephrotoxicity of DDP treatment through the P38MAPK signaling pathway. Conclusion: Cur in combination with DDP may be considered as a beneficial combination regimen for enhancing DDP sensitivity and providing a promising renoprotective effect against nephrotoxicity induced by DDP.

Selenium deficiency induces duodenal villi cell apoptosis via an oxidative stress-induced mitochondrial apoptosis pathway and an inflammatory signaling-induced death receptor pathway

Metallomics ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1390-1400 ◽  
Author(s):  
Jianfa Wang ◽  
Zhe Liu ◽  
Xianjing He ◽  
Shuai Lian ◽  
Jianbin Liang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Trace Element ◽  
Cell Apoptosis ◽  
Death Receptor ◽  
Selenium Deficiency ◽  
Mitochondrial Apoptosis ◽  
Inflammatory Signaling ◽  
Apoptosis Pathway ◽  
Death Receptor Pathway ◽  
Mitochondrial Apoptosis Pathway

Selenium is an important nutritional trace element possessing antioxidant and anti-apoptotic properties in intestinal.

scholarly journals Biomarker-driven strategy for MCL1 inhibition in T-cell lymphomas

Blood ◽  
2019 ◽  
Vol 133 (6) ◽  
pp. 566-575 ◽  
Author(s):  
Raphael Koch ◽  
Amanda L. Christie ◽  
Jennifer L. Crombie ◽  
Adam C. Palmer ◽  
Deborah Plana ◽  
...  
Keyword(s):  
T Cell ◽  
Functional Dependence ◽  
Single Agent ◽  
Apoptosis Pathway ◽  
Bh3 Mimetics ◽  
Mitochondrial Apoptosis Pathway ◽  
Bcl2 Family ◽  
T Cell Lymphomas

Abstract There is a pressing need for more effective therapies to treat patients with T-cell lymphomas (TCLs), including first-line approaches that increase the response rate to cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) chemotherapy. We characterized the mitochondrial apoptosis pathway in cell lines and patient-derived xenograft (PDX) models of TCL and assessed the in vitro efficacy of BH3 mimetics, including the BCL2 inhibitor venetoclax, the BCL2/BCL-xL inhibitor navitoclax, and the novel MCL1 inhibitor AZD5991. The abundance of antiapoptotic BCL2 family members based on immunoblotting or RNA transcript levels correlated poorly with the activity of BH3 mimetics. In contrast, the functional approach BH3 profiling reliably predicted sensitivity to BH3 mimetics in vitro and in vivo. We used BH3 profiling to select TCL PDX that were dependent on MCL1. Mice xenografted with these PDX and treated with AZD5991 had markedly improved survival. The combination of AZD5991 and CHOP achieved synergy based on survival improvement beyond a mathematical “sum of benefits” model. Thus, MCL1 inhibition is a promising strategy as both a single agent and in combination with chemotherapy for patients with TCL and functional dependence on MCL1.

scholarly journals Genistein sensitizes sarcoma cells in vitro and in vivo by enhancing apoptosis and by inhibiting DSB repair pathways

2016 ◽  
Vol 57 (3) ◽  
pp. 227-237 ◽  
Author(s):  
X.X. Liu ◽  
C. Sun ◽  
X.D. Jin ◽  
P. Li ◽  
X.G. Zheng ◽  
...  
Keyword(s):  
Strand Break ◽  
X Rays ◽  
Dsb Repair ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Repair Pathways ◽  
Non Homologous End Joining ◽  
Sarcoma Cells

Abstract The aim of this work was to investigate the radiosensitization effects of genistein on mice sarcoma cells and the corresponding biological mechanisms in vitro and in vivo . Using the non-toxic dosage of 10 μM genistein, the sensitizer enhancement ratios after exposure to X-rays at 50% cell survival (IC 50 ) was 1.45 for S180 cells. For mice cotreated with genistein and X-rays, the excised tumor tissues had reduced blood vessels and decreased size and volume compared with the control and irradiation-only groups. Moreover, a significant increase in apoptosis was accompanied by upregulation of Bax and downregulation of Bcl-2 in the mitochondria, and lots of cytochrome c being transferred to the cytoplasm. Furthermore, X-rays combined with genistein inhibited the activity of DNA-PKcs, so DNA-injured sites were dominated by Ku70/80, leading to incompleteness of homologous recombination (HR) and non-homologous end-joining (NHEJ) repairs and the eventual occurrence of cell apoptosis. Our study, for the first time, demonstrated that genistein sensitized sarcoma cells to X-rays and that this radiosensitizing effect depended on induction of the mitochondrial apoptosis pathway and inhibition of the double-strand break (DSB) repair pathways.

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