Oxidovanadium(IV) Complex Disrupts Mitochondrial Membrane Potential and Induces Apoptosis in Pancreatic Cancer Cells

2020 ◽  
Vol 21 (1) ◽  
pp. 71-83
Author(s):  
Szymon Kowalski ◽  
Aleksandra Tesmar ◽  
Artur Sikorski ◽  
Iwona Inkielewicz-Stępniak
Keyword(s):  
Pancreatic Cancer ◽  
Membrane Potential ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Vanadium Complexes ◽  
Pancreatic Cancer Cells

Background: At the present time, there is a growing interest in metal-based anticancer agents. Metal complexes exhibit many valuable clinical properties, however, due to toxicity, only a few clinically useful complexes have been discovered. It has been demonstrated that synthetic vanadium complexes exhibit many biological activities, including anti-cancer properties, however, cellular and molecular mechanisms still are not fully understood. Objective: This investigation examined the potential effects of three newly synthesized oxidovanadium(IV) complexes with 2-amino-3-hydroxypyridine against pancreatic cancer cells. Methods: We measured cytotoxicity by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, antiproliferative activity by bromodeoxyuridine assay and necrosis as well as late apoptosis by lactate dehydrogenase assay. Reactive oxygen species generation, apoptosis and mitochondrial membrane potential were determined by a flow cytometry technique. Cell morphology was evaluated by using a transmission electron microscope. Results: The results showed that oxidovanadium(IV) complexes were cytotoxic on pancreatic cancer cells (PANC-1 and MIA PaCa2) over the concentration range of 12.5-200μM, following 48h incubation. Additionally, the cellular mechanism of cytotoxic activity of [2-NH2-3-OH(py)H]4[V2O2(pmida)2]·6H2O (V3) complex was dependent on ROS generation, induction apoptosis with simultaneous disruption of mitochondrial membrane potential. Conclusion: We have proven that oxidovanadium (IV) complexes show therapeutic potential in pancreatic cancer therapy. The results of our research will help to understand the cellular mechanisms of the cytotoxic activity of the vanadium complexes and will allow a more effective design structure of new vanadium-based compounds in the future.

scholarly journals Nobiletin Inhibits Cell Growth, Migration and Invasion, and Enhances the Anti-Cancer Effect of Gemcitabine on Pancreatic Cancer Cells

2021 ◽  
Vol 16 (4) ◽  
pp. 1934578X2110040
Author(s):  
Xiang Ren ◽  
Yuran Ma ◽  
Xiao Wang ◽  
Xuetao Xu ◽  
Panpan Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Pancreatic Cancer Cells ◽  
Underlying Mechanisms ◽  
Sphere Formation

Natural products are very promising adjuvants with a variety of biological activities. Nobiletin, a citrus polymethoxyflavone, has been shown to exert an anticancer effect in various cell lines. In this study, we investigated the effects of nobiletin on cell viability, sphere formation, migration and invasion of pancreatic cancer cells, and the underlying mechanisms. Our results demonstrate that nobiletin significantly inhibited PANC-1 cell migration and invasion, and these effects were associated with downregulation of MMP-2. We also found that nobiletin, in a low concentration, exhibited a strong inhibitory effect on sphere formation. The potential molecular mechanisms were related to significant downregulation of p-mTOR and p-STAT3. Furthermore, we found that nobiletin combined with gemcitabine synergistically inhibited PANC-1 cell viability and sphere formation. The underlying mechanisms of the synergistic inhibition on growth were associated with decreases in p-STAT3 expression. Overall, our results suggest that nobiletin may be a promising candidate for pancreatic cancer adjuvant treatment.

scholarly journals Agrimoniin Sensitizes Pancreatic Cancer to Apoptosis through ROS-Mediated Energy Metabolism Dysfunction

2021 ◽  
Author(s):  
Xiandong Zhu ◽  
Feixiang Duan ◽  
Yongqiang Wang ◽  
Hewei Zhang ◽  
Xiaowu Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Flow Cytometry ◽  
Membrane Potential ◽  
Energy Metabolism ◽  
Western Blot ◽  
Cancer Cells ◽  
Mitochondrial Membrane ◽  
Cell Metabolism ◽  
Pancreatic Cancer Cells

Abstract Background Agrimoniin, a polyphenol compounds isolated from Agrimonia pilosa ledeb, has antiviral, antimicrobial, and anticancer activities in vivo and in vitro. However, its molecular mechanism in pancreatic cancer remains to be determined. Methods The proliferation was detected by colony formation, cell proliferation and toxicity, and real-time cell analysis techniques. The apoptosis was detected by flow cytometry and Western blot. Flow cytometry was used to measure the level of reactive oxygen species (ROS) and apoptosis. The level of intracellular ROS or mitochondrial membrane potential was measured with a DCFH-DA or JC-1 probe. Cell metabolism assays were analyzed and evaluated by using Agilent Seahorse Bioscience XF96 Extracellular Flux Analyzer. The target proteins were analyzed by Western blot. Subcutaneous cancer models in nude mice were established to evaluate the anticancer effects in vivo. Results Agrimoniin inhibited cell growth and promoted cell apoptosis by regulating cell metabolism in pancreatic cancer cells. Agrimoniin increased the ROS level in pancreatic cancer cells by suppressing Nrf2-dependent ROS scavenging system and disrupting normal mitochondrial membrane potential. We also found that agrimoniin significantly disrupted mitochondrial function and reduced the protein expression of mTOR/HIF-1α pathway and subsequently decreased oxygen consumption rate and extracellular acidification rate. Eventually, agrimoniin affected intracellular energy metabolism and induced apoptosis of pancreatic cancer cells. Conclusions These findings reveal the novel function of agrimoniin in promoting apoptosis of pancreatic cancer cells through mediating energy metabolism dysfunction.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

2019 ◽  
Vol 18 (9) ◽  
pp. 1313-1322 ◽  
Author(s):  
Manjula Devi Ramamoorthy ◽  
Ashok Kumar ◽  
Mahesh Ayyavu ◽  
Kannan Narayanan Dhiraviam
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

The repopulating cancer cells in melanoma are characterized by increased mitochondrial membrane potential

2016 ◽  
Vol 382 (2) ◽  
pp. 186-194 ◽  
Author(s):  
Don G. Lee ◽  
Beom K. Choi ◽  
Young H. Kim ◽  
Ho S. Oh ◽  
Sang H. Park ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane

scholarly journals Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells

2015 ◽  
Vol 46 (4) ◽  
pp. 1849-1857 ◽  
Author(s):  
RANGANATHA R. SOMASAGARA ◽  
GAGAN DEEP ◽  
SANGEETA SHROTRIYA ◽  
MANISHA PATEL ◽  
CHAPLA AGARWAL ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Bitter Melon ◽  
Gemcitabine Resistance ◽  
Pancreatic Cancer Cells

scholarly journals Mechanism of apoptosis induced by quinoxalone from the myxobacterium Stigmatella eracta WXNXJ-B in B16 mouse melanoma cell line

2017 ◽  
Author(s):  
Dahong Wang ◽  
Lanlan Wei ◽  
Shuaiying Zhang
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Biological Activities ◽  
Chromatin Condensation ◽  
Fluorescent Microscopy ◽  
Dependent Manner ◽  
Dna Ladder ◽  
Mouse Melanoma ◽  
B16 Mouse Melanoma

The biological activities of quinoxalone, a novel small molecular substance isolated from the broth of the myxobacterium Stigmatella eracta WXNXJ-B, was investigated. This study was designed to determine the anti-proliferative, apoptotic property of quinoxalone, using B16 mouse melanoma cells as a model system. The results showed that quinoxalone has antitumor activity and can significantly inhibit the proliferation of B16 cells. The extent and the timing of apoptosis were strongly dependent on the dose. After treating with quinoxalone and staining with Hoechst 33342, B16 cells showed typical apoptotic morphological features such as chromatin condensation by fluorescent microscopy. DNA isolated from B16 cells cultured with quinoxalone showed a typical DNA ladder of apoptosis in agarose gel electrophoresis. Further investigation results showed that the apoptotic machinery of B16 induced by quinoxalone was associated with drop in mitochondrial membrane potential from 5.35% to 23.7%, up-regulation of Bax and down-regulation of Bcl-2 in a dose-dependent manner. And a significant increased activation of caspase-3. Our finding suggests that quinoxalone could suppress the growth of B16 cells and reduces cell survival via disturbing mitochondrial membrane potential and inducing apoptosis of tumor cells.

scholarly journals Quantitative analysis of mitochondrial membrane potential heterogeneity in unsynchronized and synchronized cancer cells

2020 ◽  
Vol 35 (1) ◽  
Author(s):  
Amandine Rovini ◽  
Kareem Heslop ◽  
Elizabeth G. Hunt ◽  
Morgan E. Morris ◽  
Diana Fang ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Quantitative Analysis ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane
Sign in / Sign up

Export Citation Format

Share Document