Apigenin attenuates patulin-induced apoptosis in HEK293 cells by modulating ROS-mediated mitochondrial dysfunction and caspase signal pathway

Shin

et al. 2018

Phytotherapy Research

Though Tanshinone I (Tan I), a phenolic compound from Salvia miltiorrhiza, is known to have anticancer activity in several cancers, its anticancer mechanisms are not fully understood in colon cancer cells. Thus, in the present study, the underlying molecular mechanism of Tan I was explored in HCT116 and HT29 colorectal cancer cells (CRCs). Here, Tan I suppressed viability in HCT116 and HT29 cells in a time- and dose-dependent manner. Also, Tan I increased the number of terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and sub-G1 population in HCT116 and HT29 cells. Consistently, Tan I cleaved poly (adenosine diphosphate-ribose) polymerase (PARP) and caspase-8, caspase-3, attenuated the expression of Bid and activated tBid as a caspase-8 substrate and activated phosphorylation of p38 MAPK in HCT116and HT29 cells. Of note, Tan I generated reactive oxygen species (ROS) and conversely an ROS scavenger, N-acetyl- -cysteine, reversed ROS production, PARP cleavage, caspase-3 activation, and p38 MAPK phosphorylation induced by Tan I in HCT116 cells. Furthermore, p38 MAPK inhibitor SB203580 reduced cytotoxicity, increase of TUNEL-positive cells, cleavages of PARP and caspase-3 induced by Tan I in HCT116 cells. Overall, our findings for the first time suggest that ROS-dependent activation of p38 MAPK and caspase-3 is critically involved in Tan I induced apoptosis in CRCs as a potent anticancer agent.

Section: Resultsmentioning

confidence: 99%

“…Accumulating evidences reveal that apoptosis is mediated by ROS in several cancers (Chang, Xing, & Yu, 2014;Kim & Chung, 2007;Zhong…”

Section: Tan I-activated Phosphorylation Of P38 Mapk Through Ros Gementioning

confidence: 99%

Reactive oxygen species‐mediated phosphorylation of p38 signaling is critically involved in apoptotic effect of Tanshinone I in colon cancer cells

Shin

et al. 2018

Phytotherapy Research

“…Baicalein, wogonin and hesperidin increased cell viability and decreased genotoxicity and casp-3 activation in mice and neural crest cells exposed to AFB 1 (Nones et al, 2013;Ueng et al, 2001). Zhong et al (2017) reported that the apigenin re-established MMP, increased Bcl-2 expression, decreased Bax, p53 activation and the cytochrome C release in human embryonic kidney cells 293 (HEK 293 cells) treated with PAT. With the addition of silymarin to their diet, mice subjected to FB 1 contaminated feed showed decreased TNF-α expression and casp-8 activation (Sozmen et al, 2014).…”

Section: Please Cite This Article As 'In Press' World Mycotoxin Journalmentioning

confidence: 99%

Mycotoxins and oxidative stress: where are we?

Silva

Bracarense

Oswald

2018

WMJ

115

Mycotoxins are the most common contaminants of food and feed worldwide and are considered an important risk factor for human and animal health. Oxidative stress occurs in cells when the concentration of reactive oxygen species exceeds the cell’s antioxidant capacity. Oxidative stress causes DNA damage, enhances lipid peroxidation, protein damage and cell death. This review addresses the toxicity of the major mycotoxins, especially aflatoxin B1, deoxynivalenol, nivalenol, T-2 toxin, fumonisin B1, ochratoxin, patulin and zearalenone, in relation to oxidative stress. It summarises the data associated with oxidative stress as a plausible mechanism for mycotoxin-induced toxicity. Given the contamination caused by mycotoxins worldwide, the protective effects of a variety of natural compounds due to their antioxidant capacities have been evaluated. We review data on the ability of vitamins, flavonoids, crocin, curcumin, green tea, lycopene, phytic acid, L-carnitine, melatonin, minerals and mixtures of anti-oxidants to mitigate the toxic effect of mycotoxins associated with oxidative stress.

“…It further suppressed the levels of p53, upregulated Bax and downregulated Bcl‐2. It caused release of cytochrome c which caused activation of caspases‐9 and caspases‐3, caspases‐6, and caspases‐7, and eventually induced apoptosis in HEK293 cells . Table encompasses the mechanisms of mitochondrial disfunctions of each mycotoxin in test systems.…”

Section: Resultsmentioning

confidence: 99%

“…In the presence of a controlled proton leak, excess oxygen consumption resulting in ROS production may lead to inappropriate damages to mitochondrial membrane lipids such as the ROS/reactive nitrogen species (RNS)‐sensitive cardiolipin, an inner mitochondrial membrane phospholipid . Toxins such as citrinin , T‐2 , butenolide , fumonisin B1 , and patulin seem to act on these pathways.…”

Section: Discussionmentioning

confidence: 99%

Mycotoxin‐assisted mitochondrial dysfunction and cytotoxicity: Unexploited tools against proliferative disorders

et al. 2018

Mitochondria are the powerhouse of cells, which upon dysfunctions may lead to several diseases. Mycotoxins are the toxic secondary metabolites from fungi which are capable of causing diseases and death in humans and animals. They have a versatile mechanism of action in biological systems and can be used as lead compounds to treat some diseases including cancer. The present work encompasses analysis on the effects of mycotoxins on mitochondrial dysfunction. Electronic databases such as PubMed, ScienceDirect, Scopus, Web of Science, and Google Scholar were thoroughly searched for up-to-date published information associated with those mycotoxins and their effect on mitochondrial dysfunction. Findings suggest that mycotoxins such as citrinin, aflatoxin, and T-2 toxin exert multi-edged sword-like effects in test systems causing mitochondrial dysfunction. Mycotoxins can induce oxidative stress even at low concentration/dose that may be one of the major causes of mitochondrial dysfunction. On the other hand, activation of apoptotic caspases and other proteins by mycotoxins may lead to apoptotic cell death. Thus, mycotoxins-mediated mitochondrial dysfunction may be related to several chronic diseases which also makes these mycotoxins considerable as lead compounds for inducing toxic effects in cells. Their cytotoxic effects on cancer cells suggest their possible application as chemotherapeutic tools. © 2018 IUBMB Life, 70(11):1084-1092, 2018.