5-Fluorouracil combined with apigenin enhances anticancer activity through mitochondrial membrane potential (ΔΨm)-mediated apoptosis in hepatocellular carcinoma

2015 ◽  
Vol 42 (2) ◽  
pp. 146-153 ◽  
Author(s):  
Xiao-Yun Hu ◽  
Ji-Yun Liang ◽  
Xue-Jun Guo ◽  
Li Liu ◽  
Ya-Bing Guo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Membrane Potential ◽  
Anticancer Activity ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane

scholarly journals Meloxicam, a Selective COX-2 Inhibitor, Mediates Hypoxia-Inducible Factor- (HIF-) 1α Signaling in Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yinghong Zhou ◽  
Xiaofeng Dong ◽  
Peng Xiu ◽  
Xin Wang ◽  
Jianrong Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Transcriptional Activation ◽  
Mitochondrial Membrane ◽  
Hypoxia Inducible Factor ◽  
Luciferase Assay ◽  
Cox 2

Hepatocellular carcinoma (HCC) is regarded as a leading cause of cancer-related deaths, and its progression is associated with hypoxia and the induction of hypoxia-inducible factor (HIF). Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, induces cell death in various malignancies. However, the underlying mechanism remains to be elucidated in HCC, especially under hypoxic conditions. The alteration of COX-2 and HIF-1α oncogenicity was evaluated in HCC specimens by tissue microarray. Cell viability, angiogenesis assays, and xenografted nude mice were used to evaluate the effects of meloxicam, along with flow cytometry to detect the cell cycle, apoptosis, and mitochondrial membrane potential (ΔΨm) of HCC. qRT-PCR, Western blotting, immunofluorescence, immunohistochemistry, luciferase assay, and RNAi were carried out to determine the HIF-1α signaling affected by meloxicam. In this study, we showed that meloxicam exerts antiproliferative and antiangiogenesis efficacy in vitro and in vivo and causes disruption of mitochondrial membrane potential (ΔΨm), thus leading to caspase-dependent apoptosis under hypoxic environments. Exposure to meloxicam significantly reduced HIF-1α transcriptional activation and expression through sequestering it in the cytoplasm and accelerating degradation via increasing the von Hippel-Lindau tumor suppressor protein (pVHL) in HCC. These data demonstrated that inhibition of HIF-1α by meloxicam could suppress angiogenesis and enhance apoptosis of HCC cells. This discovery highlights that COX-2 specific inhibitors may be a promising therapy in the treatment of HCC.

scholarly journals Autoregulatory Feedback Mechanism of P38MAPK/Caspase-8 in Photodynamic Therapy-Hydrophilic/Lipophilic Tetra-α-(4-carboxyphenoxy) Phthalocyanine Zinc-Induced Apoptosis of Human Hepatocellular Carcinoma Bel-7402 Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Wang ◽  
Chunhui Xia ◽  
Wei Chen ◽  
Yuhang Chen ◽  
Yiyi Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Photodynamic Therapy ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Human Hepatocellular Carcinoma ◽  
Caspase 8 ◽  
Induced Apoptosis

Photodynamic therapy (PDT) is a novel and promising antitumor treatment. Our previous study showed that hydrophilic/lipophilic tetra-α-(4-carboxyphenoxy) phthalocyanine zinc- (TαPcZn-) mediated PDT (TαPcZn-PDT) inhibits the proliferation of human hepatocellular carcinoma Bel-7402 cells by triggering apoptosis and arresting cell cycle. However, mechanisms of TαPcZn-PDT-induced apoptosis of Bel-7402 cells have not been fully clarified. In the present study, therefore, effect of TαPcZn-PDT on apoptosis, P38MAPK, p-P38MAPK, Caspase-8, Caspase-3, Bcl-2, Bid, Cytochrome c, and mitochondria membrane potential in Bel-7402 cells without or with P38MAPK inhibitor SB203580 or Caspase-8 inhibitor Ac-IEFD-CHO was investigated by haematoxylin and eosin (HE) staining assay, flow cytometry analysis of annexin V-FITC/propidium iodide (PI) double staining cells and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1), and immunoblot assay. We found that TαPcZn-PDT resulted in apoptosis induction, activation of P38MAPK, Caspase-8, Caspase-3, and Bid, downregulation of Bcl-2, release of Cytochrome c from mitochondria, and disruption of mitochondrial membrane potential in TαPcZn-PDT-treated Bel-7402 cells. In contrast, SB203580 or Ac-IEFD-CHO attenuated induction of apoptosis, activation of P38MAPK, Caspase-8, Caspase-3, and Bid, downregulation of Bcl-2, release of Cytochrome c from mitochondria, and disruption of mitochondrial membrane potential in TαPcZn-PDT-treated Bel-7402 cells. Taken together, we conclude that Caspase-3, Bcl-2, Bid, and mitochondria are involved in autoregulatory feedback of P38MAPK/Caspase-8 during TαPcZn-PDT-induced apoptosis of Bel-7402 cells.

scholarly journals Brevilaterin B from Brevibacillus laterosporus has selective antitumor activity and induces apoptosis in epidermal cancer

2021 ◽  
Author(s):  
Zhou Chen ◽  
Lulu Wang ◽  
Yangliu Liu ◽  
Panpan Han ◽  
Dan Hong ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Anticancer Activity ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Morphological Characteristics ◽  
Annexin V ◽  
Dependent Manner ◽  
A431 Cells ◽  
Main Site ◽  
Brevibacillus Laterosporus

Abstract Brevibacillus laterosporus, a newly discovered genus, had been shown to be one of the best candidates for producing multiple antimicrobial peptides (AMPs). Herein, we discovered a new bioactivity of Brevilaterin B, an AMP produced by Br. laterosporus S62-9, and investigated the details about its Anticancer. Proliferation, membrane permeability and apoptotic rate were checked using CCK-8 Assay, LDH Assay and Annexin V-FITC/PI Kits. ROS levels and mitochondrial membrane potential were detected using the fluorescent probe DCFH-DA and JC-1. Brevilaterin B exhibited broad anticancer activity in a dose-dependent manner. It selectively inhibited the proliferation of epidermal cancer cell A431 but had no effect on normal cells at 2 µg/mL. Typical morphological characteristics of apoptosis and an apoptotic ratio of 71.0% in A431 were observed after treatment with 2-3 µg/mL of Brevilaterin B. In A431 cells, 21.3% ROS generated and 48.8% reduction in mitochondrial membrane potential further occurred, indicating the main site of action was the mitochondrion. Brevilaterin B secreted by Br. laterosporus S62-9 has potential application as an anticancer medicament, increasing its commercial value. It’s believed to be the first report of the anticancer activity of this type of AMPs.

Characterization of Cepharanthin Nanosuspensions and Evaluation of Their In Vitro Activity for the HepG2 Hepatocellular Carcinoma Cell Line

2020 ◽  
Vol 20 (18) ◽  
pp. 2293-2303
Author(s):  
Yue Zhao ◽  
Tingting Fu ◽  
Gaoke Meng ◽  
Fangxia Qiao ◽  
Yanhui Hou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Particle Size ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Therapeutic Agents ◽  
Glycol Succinate ◽  
Wet Milling ◽  
Cellular Apoptosis

Background: Conventional cancer therapeutics has enormous toxicity and severe side effects that generate multi-drug resistance. Therefore, an urgent need exists for new alternative therapeutic agents for cancer treatment. Cepharanthin (CEP) has anti-cancer potential but has poor aqueous solubility, which limits its clinical use. Nanosuspensions (NS) are attractive as insoluble drug delivery systems. Objectives: In this study, we used D-alpha Tocopherol acid Polyethylene Glycol Succinate (TPGS), Polyvinylpyrrolidone (PVP) VA64, and Croscamellose Sodium (CCS) as stabilizers to produce TPGS-CEP-NS, PVP VA64-CEP-NS, and CCS-CEP-NS by wet-milling technology, and then characterized the NS and evaluated their functional activities in vitro. Methods: EP Nanosuspensions (CEP-NS) were prepared by the wet-milling method. The prepared NS were characterized by particle size distribution, zeta potential, morphology, surface properties, and molecular interactions. The NS were evaluated for their effects on HepG2 cells in vitro. The evaluations included assessment of cellular cytotoxicity, cellular apoptosis, NS uptake by cells, and mitochondrial membrane potential changes. Results: CEP-NS showed an appropriate particle size and were physically stable. All CEP-NS exhibited HepG2 enhanced anti-proliferative effects by reducing cell viability, enhanced cellular uptake, induced cellular apoptosis, and mitochondrial membrane potential loss. Conclusion: : CEP-NS may be effective therapeutic agents for the treatment of hepatocellular carcinoma.

Sign in / Sign up

Export Citation Format

Share Document