Melatonin triggers the anticancer potential of phenylarsine oxide via induction of apoptosis through ROS generation and JNK activation

Metallomics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 396-407 ◽  
Author(s):  
Shahbaz Ahmad Zakki ◽  
Jibran Sualeh Muhammad ◽  
Jin-Long Li ◽  
Lu Sun ◽  
Meng-Ling Li ◽  
...  
Keyword(s):  
Endogenous Hormone ◽  
Ros Generation ◽  
Phenylarsine Oxide ◽  
Antiproliferative Effects ◽  
Induction Of Apoptosis ◽  
Jnk Activation

Melatonin, a safe endogenous hormone and a natural supplement, has recently been recognized to have antiproliferative effects and the ability to sensitize cells to other anticancer therapies.

scholarly journals Acetylshikonin Induces Apoptosis in Human Colorectal Cancer HCT-15 and LoVo Cells via Nuclear Translocation of FOXO3 and ROS Level Elevation

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Heui Min Lim ◽  
Jongsung Lee ◽  
Myeong Jin Nam ◽  
See-Hyoung Park
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Human Colorectal Cancer ◽  
Antiproliferative Effects ◽  
Lovo Cells ◽  
Colorectal Cancer Cells

Acetylshikonin, a naphthoquinone, is a pigment compound derived from Arnebia sp., which is known for its anti-inflammatory potential. However, its anticarcinogenic effect has not been well investigated. Thus, in this study, we focused on investigating its apoptotic effects against HCT-15 and LoVo cells, which are human colorectal cancer cells. MTT assay, cell counting assay, and colony formation assay have shown acetylshikonin treatment induced cytotoxic and antiproliferative effects against colorectal cancer cells in a dose- and time-dependent manner. DNA fragmentation was observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Also, the increase of subG1 phase in cell cycle arrest assay and early/late apoptotic rates in annexin V/propidium iodide (PI) double staining assay was observed, which indicates an apoptotic potential of acetylshikonin against colorectal cancer cells. 2 ′ ,7 ′ -Dichlorofluorescin diacetate (DCF-DA) staining was used to evaluate reactive oxygen species (ROS) generation in acetylshikonin-treated colorectal cancer cells. Fluorescence-activated cell sorting (FACS) analysis showed that acetylshikonin induced an increase in reactive oxygen species (ROS) levels and apoptotic rate in a dose- and time-dependent manner in HCT-15 and LoVo cells. In contrast, cotreatment with N-acetyl cysteine (NAC) has reduced ROS generation and antiproliferative effects in colorectal cancer cells. Western blotting analysis showed that acetylshikonin treatment induced increase of cleaved PARP, γH2AX, FOXO3, Bax, Bim, Bad, p21, p27, and active forms of caspase-3, caspase-7, caspase-9, caspase-6, and caspase-8 protein levels, while those of inactive forms were decreased. Also, the expressions of pAkt, Bcl-2, Bcl-xL, peroxiredoxin, and thioredoxin 1 were decreased. Furthermore, western blotting analysis of cytoplasmic and nuclear fractionated proteins showed that acetylshikonin treatment induced the nuclear translocation of FOXO3, which might result from DNA damage by the increased intracellular ROS level. This study represents apoptotic potential of acetylshikonin against colorectal cancer cells via translocation of FOXO3 to the nucleus and upregulation of ROS generation.

scholarly journals Agaricus blazeiExtract Induces Apoptosis through ROS-Dependent JNK Activation Involving the Mitochondrial Pathway and Suppression of Constitutive NF-κB in THP-1 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Mun-Ock Kim ◽  
Dong-Oh Moon ◽  
Jin Myung Jung ◽  
Won Sup Lee ◽  
Yung Hyun Choi ◽  
...  
Keyword(s):  
Mitochondrial Pathway ◽  
Ros Generation ◽  
Gene Products ◽  
Oxygen Species ◽  
Agaricus Blazei ◽  
Anti Cancer ◽  
Induced Apoptosis ◽  
Jnk Activation ◽  
Apoptotic Effects ◽  
Apoptotic Mechanism

Agaricus blazeiis widely accepted as a traditional medicinal mushroom, and it has been known to exhibit immunostimulatory and anti-cancer activity. However, the apoptotic mechanism in cancer cells is poorly understood. In this study, we have investigated whetherA. blazeiextract (ABE) exerts antiproliferative and apoptotic effects in human leukemic THP-1 cells. We observed that ABE-induced apoptosis is associated with the mitochondrial pathway, which is mediated by reactive oxygen species (ROS) generation and prolonged c-Jun N-terminal kinase (JNK) activation. In addition, the ABE treatment resulted in the accumulation of cytochromecin the cytoplasm, an increase in caspase activity, and an upregulation of Bax and Bad. With those results in mind, we found that ABE decreases constitutive NF-κB activation and NF-κB-regulated gene products such as IAP-1 and -2. We concluded that ABE induces apoptosis with ROS-dependent JNK activation and constitutive activated NF-κB inhibition in THP-1 cells.

scholarly journals REDOX Reaction at ASK1-Cys250 Is Essential for Activation of JNK and Induction of Apoptosis

2009 ◽  
Vol 20 (16) ◽  
pp. 3628-3637 ◽  
Author(s):  
Philippe J. Nadeau ◽  
Steve J. Charette ◽  
Jacques Landry
Keyword(s):  
Oxidative Stress ◽  
Disulfide Bonds ◽  
Reductase Activity ◽  
The Other ◽  
Activation Loop ◽  
Cysteine Oxidation ◽  
Jnk Pathway ◽  
Induction Of Apoptosis ◽  
Thiol Reductase ◽  
Jnk Activation

ASK1 cysteine oxidation allows JNK activation upon oxidative stress. Trx1 negatively regulates this pathway by reducing the oxidized cysteines of ASK1. However, precisely how oxidized ASK1 is involved in JNK activation and how Trx1 regulates ASK1 oxidoreduction remains elusive. Here, we describe two different thiol reductase activities of Trx1 on ASK1. First, in H2O2-treated cells, Trx1 reduces the various disulfide bonds generated between cysteines of ASK1 by a rapid and transient action. Second, in untreated cells, Trx1 shows a more stable thiol reductase activity on cysteine 250 (Cys250) of ASK1. After H2O2 treatment, Trx1 dissociates from Cys250, which is not sufficient to activate the ASK1-JNK pathway. Indeed, in untreated cells, a Cys250 to alanine mutant of ASK1 (C250A), which cannot bind Trx1, does not constitutively activate JNK. On the other hand, in H2O2-treated cells, this mutant (C250A) fails to activate JNK and does not induce apoptosis, although it remains fully phosphorylated on Threonine 838 (Thr838) in its activation loop. Overall, our data show that Cys250 is essential for H2O2-dependent signaling downstream from ASK1 but at a step subsequent to the phosphorylation of ASK1 Thr838. They also clarify the thiol reductase function of Trx1 on ASK1 activity.

scholarly journals Annurca apple polyphenol extract selectively kills MDA-MB-231 cells through ROS generation, sustained JNK activation and cell growth and survival inhibition

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elisa Martino ◽  
Daniela Cristina Vuoso ◽  
Stefania D’Angelo ◽  
Luigi Mele ◽  
Nunzia D’Onofrio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Ros Generation ◽  
Growth And Survival ◽  
Phase Arrest ◽  
M Phase ◽  
Jnk Activation

Abstract Polyphenols represent the most studied class of nutraceuticals that can be therapeutics for a large spectrum of diseases, including cancer. In this study, we investigated for the first time the antitumor activities of polyphenol extract from Annurca apple (APE) in MDA-MB-231 triple negative breast cancer cells, and we explored the underlying mechanisms. APE selectively inhibited MDA-MB-231 cell viability and caused G2/M phase arrest associated with p27 and phospho-cdc25C upregulation and with p21 downregulation. APE promoted reactive oxygen species (ROS) generation in MDA-MB-231 cells while it acted as antioxidant in non-tumorigenic MCF10A cells. We demonstrated that ROS generation represented the primary step of APE antitumor activity as pretreatment with antioxidant N-acetylcysteine (NAC) prevented APE-induced G2/M phase arrest, apoptosis, and autophagy. APE downregulated Dusp-1 and induced a significant increase in JNK/c-Jun phosphorylation that were both prevented by NAC. Moreover, downregulation of JNK by its specific inhibitor SP600125 significantly diminished the anticancer activity of APE indicating that ROS generation and sustained JNK activation represented the main underlying mechanism of APE-induced cell death. APE also inhibited AKT activation and downregulated several oncoproteins, such as NF-kB, c-myc, and β-catenin. In light of these results, APE may be an attractive candidate for drug development against triple negative breast cancer.

scholarly journals Induction of Apoptosis by Costunolide in Bladder Cancer Cells is Mediated through ROS Generation and Mitochondrial Dysfunction

Molecules ◽  
2013 ◽  
Vol 18 (2) ◽  
pp. 1418-1433 ◽  
Author(s):  
Azhar Rasul ◽  
Rui Bao ◽  
Mahadev Malhi ◽  
Bing Zhao ◽  
Ichiro Tsuji ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Ros Generation ◽  
Bladder Cancer Cells ◽  
Induction Of Apoptosis

scholarly journals Anastatica hierochuntica (L.) methanolic and aqueous extracts exert antiproliferative effects through the induction of apoptosis in MCF-7 breast cancer cells

2020 ◽  
Vol 28 (8) ◽  
pp. 985-993
Author(s):  
Saranya Rameshbabu ◽  
Safia A. Messaoudi ◽  
Zeyad Ibrahim Alehaideb ◽  
Mohammed Syed Ali ◽  
Anuradha Venktraman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Aqueous Extracts ◽  
Antiproliferative Effects ◽  
Induction Of Apoptosis ◽  
Mcf 7
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