Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation

Chae, Jung‐Il; Cho, Jin Hyoung; Kim, Dong Joon; Lee, Kyung-Ae; Cho, Moon‐Kyun; Nam, Heerim; Woo, Kee-Min; Lee, Sang‐Han; Shim, Jung‐Hyun

doi:10.3892/ijmm.2012.969

Cited by 6 publications

(2 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous studies have demonstrated the ability of juglone to inhibit the PIK3/Akt cascade, but Chae et al [ 101 ] linked the inhibition of this pathway with the ability of juglone to avoid the differentiation of normal JB6 Cl 41 skin cells under the effect of the cancer promoters 12- O -tetradecanoylphorbol-13-acetate (TPA) and endothelial growth factors. This suggests that juglone blocks several of the molecular pathways that are involved in cancer development.…”

Section: Anticancer Activitymentioning

confidence: 99%

Natural Products to Fight Cancer: A Focus on Juglans regia

Catanzaro

Greco

Potenza

et al. 2018

Toxins

View full text Add to dashboard Cite

Even if cancer represents a burden for human society, an exhaustive cure has not been discovered yet. Low therapeutic index and resistance to pharmacotherapy are two of the major limits of antitumour treatments. Natural products represent an excellent library of bioactive molecules. Thus, tapping into the natural world may prove useful in identifying new therapeutic options with favourable pharmaco-toxicological profiles. Juglans regia, or common walnut, is a very resilient tree that has inhabited our planet for thousands of years. Many studies correlate walnut consumption to beneficial effects towards several chronic diseases, such as cancer, mainly due to the bioactive molecules stored in different parts of the plant. Among others, polyphenols, quinones, proteins, and essential fatty acids contribute to its pharmacologic activity. The present review aims to offer a comprehensive perspective about the antitumour potential of the most promising compounds stored in this plant, such as juglanin, juglone, and the ellagitannin-metabolites urolithins or deriving from walnut dietary intake. All molecules and a chronic intake of the fruit provide tangible anticancer effects. However, the scarcity of studies on humans does not allow results to be conclusive.

show abstract

Section: Anticancer Activitymentioning

confidence: 99%

Natural Products to Fight Cancer: A Focus on Juglans regia

Catanzaro

Greco

Potenza

et al. 2018

Toxins

View full text Add to dashboard Cite

show abstract

“…The involved mechanisms are similar but not necessarily identical [ 12 ]. Eryptosis is stimulated by a wide variety of chemicals [ 14 , 23 , 24 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ] and excessive eryptosis is observed in several clinical conditions, including sepsis, fever, malaria, sickle cell disease, thalassemia, Wilson’s disease, iron deficiency, hepatic failure, malignancy, metabolic syndrome, diabetes, dehydration, renal insufficiency, hemolytic uremic syndrome, hyperphosphatemia and phosphate depletion [ 12 , 66 , 67 ].…”

Section: Introductionmentioning

confidence: 99%

Triggering of Programmed Erythrocyte Death by Alantolactone

Alzoubi

Calabrò

Egler

et al. 2014

Toxins

View full text Add to dashboard Cite

The sesquiterpene alantolactone counteracts malignancy, an effect at least in part due to stimulation of suicidal death or apoptosis of tumor cells. Signaling of alantolactone induced apoptosis involves altered gene expression and mitochondrial depolarization. Erythrocytes lack mitochondria and nuclei but may enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Cellular mechanisms involved in triggering of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i) and oxidative stress. The present study explored, whether alantolactone stimulates eryptosis. To this end, erythrocyte volume was estimated from forward scatter, phosphatidylserine-exposure at the erythrocyte surface from FITC-annexin-V-binding, [Ca2+]i from Fluo3-fluorescence, ceramide abundance from binding of fluorescent antibodies, and oxidative stress from 2',7'-dichlorodihydrofluorescein-diacetate (DCFDA) fluorescence. As a result, a 48 h exposure of human erythrocytes to alantolactone (≥20 μM) significantly decreased erythrocyte forward scatter and increased the percentage of annexin-V-binding cells. Alantolactone significantly increased Fluo3 fluorescence (60 μM), ceramide abundance (60 μM) and DCFDA fluorescence (≥40 μM). The effect of alantolactone (60 μM) on annexin-V-binding was not significantly modified by removal of extracellular Ca2+. In conclusion, alantolactone stimulates suicidal erythrocyte death or eryptosis, an effect paralleled by increase of [Ca2+]i, ceramide abundance and oxidative stress.

show abstract

Augmentation of oxidative stress-induced apoptosis in MCF7 cells by ascorbate–tamoxifen and/or ascorbate–juglone treatments

Sajadimajd

Yazdanparast

Roshanzamir

2015

In Vitro Cell.Dev.Biol.-Animal

View full text Add to dashboard Cite

Since reactive oxygen species (ROS) play diverse roles in cancer, modulating the redox status of cancerous cells seems to be a promising therapeutic approach. Oxidant-targeted therapy appears logical for intervention with the acquired adaptive response to oxidative stress in cancer. In this study, we investigated the cytotoxic effects of juglone (J) and tamoxifen (T) and also the combination of each with ascorbate (A): tamoxifen/ascorbate (TA) and/or juglone/ascorbate (JA) on MCF7 cancerous cells. The results revealed that the growth inhibitory effects of juglone and tamoxifen were each associated with enhanced levels of ROS production and lipid peroxidation. These effects were markedly intensified in tamoxifen/ascorbate and juglone/ascorbate co-treatments. On the other hand, the intracellular anti-oxidant components such as reduced glutathione (GSH), catalase, superoxide dismutase (SOD), and glutathione peroxidase significantly declined in cells subjected to combination treatments compared to that in cells exposed solely to tamoxifen, juglone, and the untreated control cells. In addition, ascorbate association induced more apoptotic and necrotic or necrotic-like cell death than cells treated with each drug alone. These results were further confirmed by comparing the Bax/Bcl2 ratio in combination-treated cells. Additionally, ascorbate was able to potentiate the cytotoxic effects of combination therapy via activation of ROS-responsive factors including Foxo family members.

show abstract

Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation

Cited by 6 publications

References 37 publications

Natural Products to Fight Cancer: A Focus on Juglans regia

Natural Products to Fight Cancer: A Focus on Juglans regia

Triggering of Programmed Erythrocyte Death by Alantolactone

Augmentation of oxidative stress-induced apoptosis in MCF7 cells by ascorbate–tamoxifen and/or ascorbate–juglone treatments

Contact Info

Product

Resources

About