Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin

Deck, Lorraine M.; Hunsaker, Lucy A.; Jagt, Thomas A. Vander; Whalen, Lisa J.; Royer, Robert E.; Jagt, David L. Vander

doi:10.1016/j.ejmech.2017.11.048

Cited by 52 publications

(30 citation statements)

References 84 publications

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“…We recently showed that bardoxolone methyl (BM) which is a potent Nrf-2 inducer can increase the efficacy of enzalutamide in an enzalutamide-resistant PCa cell line (CWR22Rv1) by degrading both AR-FL as well as AR-V7 further underscoring the AR suppressive function of Nrf-2 [ 109 ]. This corroborates the fact that AR downregulation and Nrf-2 activation are the major pathways responsible for the anticancer efficacy of phytochemicals like SFN [ 38 , 39 , 40 , 41 , 42 ] and CUR [ 43 , 44 , 45 , 46 , 47 ] in PCa. SFN has been shown to augment expression of Nrf2 in mouse TRAMP C1 PCa cells [ 40 ] and cause transcriptional repression [ 140 ] as well as destabilization of AR in PCa cells [ 141 ].…”

Section: Interplay Between Nrf-2-antioxidant Nf-κb Inflammatory Asupporting

confidence: 84%

“…Nrf-2 has been shown to suppress growth and migration of PCa cells by upregulating ferroportin [ 36 ] and sensitize PCa cells to radiation by reducing basal ROS levels [ 37 ]. Chemoprevention by phytochemicals like sulforaphane (SFN) [ 38 , 39 , 40 , 41 , 42 ] and curcumin (CUR) [ 43 , 44 , 45 , 46 , 47 ] has been attributed to the activation of Nrf-2 pathway.…”

Section: Oxidative Stress and Prostate Cancermentioning

confidence: 99%

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Targeting Crosstalk between Nrf-2, NF-κB and Androgen Receptor Signaling in Prostate Cancer

Khurana

Sikka

2018

Cancers

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Oxidative stress, inflammation and androgen receptor (AR) signaling play a pivotal role in the initiation, development and progression of prostate cancer (PCa). Numerous papers in the literature have documented the interconnection between oxidative stress and inflammation; and how antioxidants can combat the inflammation. It has been shown in the literature that both oxidative stress and inflammation regulate AR, the key receptor involved in the transition of PCa to castration resistant prostate cancer (CRPC). In this review, we discuss about the importance of targeting Nrf-2-antioxidant signaling, NF-κB inflammatory response and AR signaling in PCa. Finally, we discuss about the crosstalk between these three critical pathways as well as how the anti-inflammatory antioxidant phytochemicals like sulforaphane (SFN) and curcumin (CUR), which can also target AR, can be ideal candidates in the chemoprevention of PCa.

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Section: Interplay Between Nrf-2-antioxidant Nf-κb Inflammatory Asupporting

confidence: 84%

Section: Oxidative Stress and Prostate Cancermentioning

confidence: 99%

Targeting Crosstalk between Nrf-2, NF-κB and Androgen Receptor Signaling in Prostate Cancer

Khurana

Sikka

2018

Cancers

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“…Thus, several studies are underway aiming to develop curcumin analogues of higher potency, better bioavailability and longer half-life. For example, allylated monocarbonyl analogues and enone analogues of curcumin were found to promote mitotic arrest and apoptosis by reactive oxygen species-mediated stress ( 27 , 28 ). Novel curcumin analogues exhibited high potency in castration-resistant prostate cancer ( 29 ) and nasopharyngeal carcinoma ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells

et al. 2018

Exp Ther Med

106

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Curcumin is a natural compound that appears to be promising for clinical application, as it has been shown in in vitro and in vivo studies to exert antitumor effects by modulating multiple signaling cellular pathways. In the present study, the antitumor effects of curcumin and its mechanism of action were investigated in cultured breast cancer cells. The MTT assay was used to determine the effect of curcumin on breast cancer cell proliferation, flow cytometry was used to detect alterations of the cell cycle, and western blot analysis was used to determine the expression of signaling molecules involved in the cell cycle, proliferation and apoptosis. The results revealed that curcumin significantly inhibited the proliferation of various breast cancer cell lines, such as T47D, MCF7, MDA-MB-231 and MDA-MB-468, with an IC50 at the micromolar level, indicating the potent antitumor activity of curcumin. In-depth study of its mechanism of action revealed that curcumin induced cell cycle arrest at the G2/M phase and decreased the expression of the CDC25 and CDC2 proteins, while increasing the expression of P21. In addition, curcumin inhibited the phosphorylation of protein kinase B (Akt)/mammalian target of rapamycin (mTOR), decreased B-cell lymphoma 2 (BCL2) and promoted BCL-2-associated X protein (BAX) and cleavage of caspase 3, subsequently inducing apoptosis of breast cancer cells. In conclusion, curcumin inhibited the proliferation of breast cancer cells and induced G2/M phase cell cycle arrest and apoptosis, which may be associated with the decrease of CDC25 and CDC2 and increase of P21 protein levels, as well as inhibition of the phosphorylation of Akt/mTOR and induction of the mitochondrial apoptotic pathway. The findings of the present study may provide a basis for the further study of curcumin in the treatment of breast cancer.

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“…Bisceglia et al [18] examined the anti-inflammatory activity of analogue AB19 and curcumin ( Figure 1). In addition, Deck et al [81] examined enone analogues of curcumin as Nrf2 activators.…”

Section: Anti-neuroinflammatory Activitymentioning

confidence: 99%

“…Further research is in progess to define the antioxidant mechanism of the derivatives (Figure 1 and Table 2). Additionally, Deck et al [81] examined enone analogues of curcumin on Nrf2 protocol to define Nrf2 activators. The tested compounds were divided into three groups presenting the following: (i) a seven-carbon dienonelinker, (ii) a five-carbon enone linker with and without a ring, and (iii) a three-carbon enone linker.…”

Section: Antioxidant Activitymentioning

confidence: 99%

Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

Chainoglou

Hadjipavlou‐Litina

2020

IJMS

113

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Worldwide, Alzheimer’s disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly preventing or treating AD. During the last decade, the scientific community has focused their research on the optimization of therapeutic properties and on the improvement of pharmacokinetic properties of curcumin. This review summarizes bibliographical data from 2009 to 2019 on curcumin analogues, derivatives, and hybrids, as well as their therapeutic, preventic, and diagnostic applications in AD. Recent advances in the field have revealed that the phenolic hydroxyl group could contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seem to contribute to the suppression of amyloid-β peptide (Aβ42) and to the suppression of amyloid precursor protein (APP) andhydrophobic interactions have also revealed a growing role. Furthermore, flexible moieties, at the linker, are crucial for the inhibition of Aβ aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The promising role of curcumin-based compounds in diagnostic imaging is highlighted. The keto-enol tautomerism seems to be a novel modification for the design of amyloid-binding agents. Molecular docking results, (Q)SAR, as well as in vitro and in vivo tests highlight the structures and chemical moieties that are correlated with specific activity. As a result, the knowledge gained from the existing research should lead to the design and synthesis ofinnovative and multitargetedcurcumin analogues, derivatives, or curcumin hybrids, which would be very useful drug and tools in medicine for both diagnosis and treatment of AD.

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Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin

Cited by 52 publications

References 84 publications

Targeting Crosstalk between Nrf-2, NF-κB and Androgen Receptor Signaling in Prostate Cancer

Targeting Crosstalk between Nrf-2, NF-κB and Androgen Receptor Signaling in Prostate Cancer

Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells

Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

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