Resveratrol induces apoptosis by directly targeting Ras-GTPase-activating protein SH3 domain-binding protein 1

Oi, Naomi; Yuan, Jian; Malakhova, Margarita; Luo, Kuntian; Li, Y.; Ryu, Joohyun; Zhang, L.; Bode, Ann M.; Xu, Zhijian; Lou, Zhenkun; Dong, Zigang

doi:10.1038/onc.2014.194

Cited by 56 publications

(62 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 times higher in HCT-116 p53-/- cells) than those determined in HCT-116 wt cells carrying a functional p53 protein (reviewed in [39]). Although similar findings have been reported for resveratrol using the same cell lines [40], the possible involvement of other (tumor suppressor) proteins or drug/membrane transporters in these processes should be further investigated.…”

Section: Discussionsupporting

confidence: 73%

Growth-Inhibiting Activity of Resveratrol Imine Analogs on Tumor Cells In Vitro

Wang¹,

Willenberg²,

Krohn

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

Although resveratrol exerts manifold antitumorigenic effects in vitro, its efficacy against malignancies in vivo seems limited. This has been increasingly recognized in recent years and has prompted scientists to search for structurally related compounds with more promising anticarcinogenic and/or pharmacokinetic properties. A class of structurally modified resveratrol derivatives, so-called resveratrol imine analogs (IRA’s), might meet these requirements. Therefore, the biological activity of five of these compounds was examined and compared to that of resveratrol. Firstly, the antiproliferative potency of all five IRA’s was investigated using the p53 wildtype-carrying colorectal carcinoma cell line HCT-116wt. Then, using the former and a panel of various other tumor cell lines (including the p53 knockout variant HCT-116p53-/-), the growth-inhibiting and cell cycle-disturbing effects of the most potent IRA (IRA 5, 2-[[(2-hydroxyphenyl)methylene]amino]-phenol) were studied as was its influence on cyclooxygenase-2 expression and activity. Finally, rat liver microsomes were used to determine the metabolic stability of that compound. IRA 5 was clearly the most potent compound in HCT-116wt cells, with an unusually high IC50-value of 0.6 μM. However, in the other five cell lines used, the antiproliferative activity was mostly similar to resveratrol and the effects on the cell cycle were heterogeneous. Although all cell lines were affected by treatment with IRA 5, cells expressing functional p53 seemed to react more sensitively, suggesting that this protein plays a modulating role in the induction of IRA 5-mediated biological effects. Lastly, IRA 5 led to contradictory effects on cyclooxygenase-2 expression and activity and was less glucuronidated than resveratrol. As IRA 5 is approximately 50 times more toxic towards HCT-116wt cells, exerts different effects on the cyclooxygenase-2 and is metabolized to a lesser extent, it shows certain advantages over resveratrol and could therefore serve as basis for additional chemical modifications, potentially yielding compounds with more favorable biological and pharmacokinetic features.

show abstract

Section: Discussionsupporting

confidence: 73%

Growth-Inhibiting Activity of Resveratrol Imine Analogs on Tumor Cells In Vitro

Wang¹,

Willenberg²,

Krohn

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Moreover, additional evidence indicates that resveratrol enhances deubiquitination and the up‐regulation of p53 through USP10 (Oi et al . ). Although it is not known whether this would represent a cardioprotective mechanism of resveratrol the present findings suggest that alleviation of apoptotic signalling induced by resveratrol in doxorubicin‐challenged aged hearts may, at least in part, be mediated by USP7 through the activation of SIRT1 deacetylase (Fig.…”

Section: Discussionmentioning

confidence: 97%

Resveratrol protects against doxorubicin‐induced cardiotoxicity in aged hearts through the SIRT1‐USP7 axis

Sin

Tam

Yung

et al. 2015

The Journal of Physiology

View full text Add to dashboard Cite

Key pointsr Doxorubicin induced functional deteriorations and elevations of USP7-related apoptotic/catabolic signalling in the senescent heart r Resveratrol protects against doxorubicin-induced alterations through the restoration of SIRT1 deacetylase activity Abstract A compromised cardiac function is often seen in elderly cancer patients receiving doxorubicin therapy. The present study tested the hypothesis that acute intervention with resveratrol, a natural anti-oxidant found in grapes and red wine, reduces the cardiotoxicity of doxorubicin through restoration of sirtuin 1 (SIRT1) deacetylase activity, and attenuation of the catabolic/apoptotic pathways orchestrated by USP7, a p53 deubiquitinating protein, using young (aged 2 months) and old (aged 10 months) senescence-accelerated mice prone 8 (SAMP8). Animals were randomised to receive saline, doxorubicin, and doxorubicin in combination with resveratrol, in the presence or absence of SIRT1 inhibitors, sirtinol or EX527. Resveratrol alone, but not in combination with either of the SIRT1 inhibitors, suppressed the doxorubicin-induced impairment of cardiac systolic function in aged animals. Doxorubicin reduced SIRT1 deacetylase activity, and elevated proteasomal activity and USP7; it also increased the protein level of p300 and ubiquitinated proteins in hearts from aged SAMP8. These doxorubicin-induced alterations were prevented by resveratrol, whereas the protective action of resveratrol was antagonised by sirtinol and EX527. In young SAMP8 hearts, resveratrol attenuated the doxorubicin-induced increases in acetylation of Foxo1 and transactivation of MuRF-1, whereas these mitigations were not found after treatment with SIRT1 inhibitors. However, the protein contents of acetylated Foxo1 and MuRF-1 were not affected by any of the drugs studied in aged SAMP8 hearts. Resveratrol also ameliorated the augmentation of pro-apoptotic markers including p53, Bax, caspase 3 activity and apoptotic DNA fragmentation induced by doxorubicin in hearts from aged animals, whereas these reductions were diminished by combined treatment with SIRT1 inhibitors. These data demonstrate that resveratrol ameliorates doxorubicin-induced cardiotoxicity in aged hearts through the restoration of SIRT1 activity to attenuate USP7-related catabolic/pro-apoptotic signalling. AbbreviationsAMPK, AMP-activated protein kinase; DR, doxorubicin + resveratrol; DRE, doxorubicin + resveratrol + EX527; DRS, doxorubicin + resveratrol + sirtinol; DV, doxorubicin and vehicle; EF, ejection fraction; FS, fractional shortening; LVEDD, left ventricle end-diastolic dimension; LVESD, left ventricle end-systolic dimension; SAMP8, senescence-accelerated mice prone 8; SC, saline control; SIRT1, sirtuin 1; TBST, Tris-buffered saline with 0.1% Tween 20; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labelling.

show abstract

“…The USP10 responsible deubiquitination is able to stimulate the anti-oncogenic activity of p53 both in renal clear cell carcinoma [93] and colorectal cancer [99], highlighting the potential significance of USP10/p53 targeted cancer treatment. Although the majority of current viewpoints agree the tumor-inhibitory role of USP10, its possibly versatile functions require future in-depth studies.…”

Section: Functions Of Ampk Signaling Components In Tumorigenesismentioning

confidence: 99%

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Cheng

Zhang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

View full text Add to dashboard Cite

AMP-activated protein kinase (AMPK) is a ubiquitously expressed metabolic sensor among various species. Specifically, cellular AMPK is phosphorylated and activated under certain stressful conditions, such as energy deprivation, in turn to activate diversified downstream substrates to modulate the adaptive changes and maintain metabolic homeostasis. Recently, emerging evidences have implicated the potential roles of AMPK signaling in tumor initiation and progression. Nevertheless, a comprehensive description on such topic is still in scarcity, especially in combination of its biochemical features with mouse modeling results to elucidate the physiological role of AMPK signaling in tumorigenesis. Hence, we performed this thorough review by summarizing the tumorigenic role of each component along the AMPK signaling, comprising of both its upstream and downstream effectors. Moreover, their functional interplay with the AMPK heterotrimer and exclusive efficacies in carcinogenesis were chiefly explained among genetically altered mice models. Importantly, the pharmaceutical investigations of AMPK relevant medications have also been highlighted. In summary, in this review, we not only elucidate the potential functions of AMPK signaling pathway in governing tumorigenesis, but also potentiate the future targeted strategy aiming for better treatment of aberrant metabolism-associated diseases, including cancer.

show abstract

Resveratrol induces apoptosis by directly targeting Ras-GTPase-activating protein SH3 domain-binding protein 1

Cited by 56 publications

References 36 publications

Growth-Inhibiting Activity of Resveratrol Imine Analogs on Tumor Cells In Vitro

Growth-Inhibiting Activity of Resveratrol Imine Analogs on Tumor Cells In Vitro

Resveratrol protects against doxorubicin‐induced cardiotoxicity in aged hearts through the SIRT1‐USP7 axis

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Contact Info

Product

Resources

About