Bioactivities of EF24, a Novel Curcumin Analog: A Review

He, Yonghan; Li, Wen; Hu, Guangrong; Sun, Hui; Kong, Qing‐Peng

doi:10.3389/fonc.2018.00614

Cited by 65 publications

(55 citation statements)

References 101 publications

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“…However, few of those clinical trials showed positive outcomes [7], mainly due to its low solubility and poor bioavailability (<1%) [8]. Demethoxycurcumin (DMC) and diphenyl difluoroketone (EF-24) are natural and synthetic CUR analogues, respectively, that display multiple potent bioactivities and increased bioavailability compared to CUR [9,10]. For example, EF-24 was reported to have higher oral bioavailability (60%) and to be much safer than a chemotherapeutic drug in mice [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, EF-24 exhibited a 10~20-fold lower 50% growth inhibitory concentration (IC 50 ) than CUR in various solid tumor cells including ovarian, cervical, lung, breast, and prostate cancer cells [13][14][15][16]. Although these two CUR analogues, EF-24 and DMC, were reported to inhibit the proliferation of various solid tumor cells in in vitro and in vivo models [9,10], the precise impacts of these analogues on non-solid tumors, particularly AML, are still unclear.…”

Section: Introductionmentioning

confidence: 99%

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The Curcumin Analogue, EF-24, Triggers p38 MAPK-Mediated Apoptotic Cell Death via Inducing PP2A-Modulated ERK Deactivation in Human Acute Myeloid Leukemia Cells

Hsiao

Chang

Lee

et al. 2020

Cancers

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Curcumin (CUR) has a range of therapeutic benefits against cancers, but its poor solubility and low bioavailability limit its clinical use. Demethoxycurcumin (DMC) and diphenyl difluoroketone (EF-24) are natural and synthetic curcumin analogues, respectively, with better solubilities and higher anti-carcinogenic activities in various solid tumors than CUR. However, the efficacy of these analogues against non-solid tumors, particularly in acute myeloid leukemia (AML), has not been fully investigated. Herein, we observed that both DMC and EF-24 significantly decrease the proportion of viable AML cells including HL-60, U937, and MV4-11, harboring different NRAS and Fms-like tyrosine kinase 3 (FLT3) statuses, and that EF-24 has a lower half maximal inhibitory concentration (IC50) than DMC. We found that EF-24 treatment induces several features of apoptosis, including an increase in the sub-G1 population, phosphatidylserine (PS) externalization, and significant activation of extrinsic proapoptotic signaling such as caspase-8 and -3 activation. Mechanistically, p38 mitogen-activated protein kinase (MAPK) activation is critical for EF-24-triggered apoptosis via activating protein phosphatase 2A (PP2A) to attenuate extracellular-regulated protein kinase (ERK) activities in HL-60 AML cells. In the clinic, patients with AML expressing high level of PP2A have the most favorable prognoses compared to various solid tumors. Taken together, our results indicate that EF-24 is a potential therapeutic agent for treating AML, especially for cancer types that lose the function of the PP2A tumor suppressor.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Curcumin Analogue, EF-24, Triggers p38 MAPK-Mediated Apoptotic Cell Death via Inducing PP2A-Modulated ERK Deactivation in Human Acute Myeloid Leukemia Cells

Hsiao

Chang

Lee

et al. 2020

Cancers

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“…In endothelial progenitor cells, MHY2233 was shown to decrease acetylated p53 and downstream p21 expression, and to increase expression of FOXO3a, a transcription factor that enhances Sirt1 transcription and leads to decreased p16 expression [197]. The curcumin analogue EF24, that also possesses senolytic activities as described thereafter, has the ability to counteract major inflammatory pathways [219].…”

Section: Msc Rejuvenating Strategiesmentioning

confidence: 97%

Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging

Neri

Borzı̀

2020

Biomolecules

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Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. Beside the fundamental in vivo role of MSCs, they have also emerged in the last years as extremely promising therapeutic agents for a wide variety of clinical conditions. MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. Aging of MSCs (both in vivo and in vitro) can affect not only their replicative potential, but also their properties, like immunomodulation and secretory profile, thus possibly compromising their therapeutic effect. It is therefore of critical importance to unveil the underlying mechanisms of MSC senescence and to define shared methods to assess MSC aging status. The present review will focus on current scientific knowledge about MSC aging mechanisms, control and effects, including possible anti-aging treatments.

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“…[16][17][18] Curcumin and its analogs EF24 and EF31 are also toxic, and there are huge defects in drug metabolism. [19][20][21] Therefore, finding a new type of IKKβ/NF-κB inhibitor with high efficiency and low toxicity, and exploring if it can reverse the resistance of gemcitabine has become our main research goal.…”

Section: Introductionmentioning

confidence: 99%

<p>Emodin Reverses Gemcitabine Resistance of Pancreatic Cancer Cell Lines Through Inhibition of IKKβ/NF-κB Signaling Pathway</p>

Tong¹,

Huang²,

Chen³

et al. 2020

OTT

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Background: Pancreatic cancer is one of the most malignant tumors, and gemcitabine has been considered as the standard treatment and been widely utilized as a first-line drug for advanced pancreatic cancer, but gemcitabine-resistance always occurs after a short period of treatment. Methods: Two pancreatic cancer cell lines Panc-1 and MIA-PaCa-2 were used as the study subject and their gemcitabine-resistant cells were established. Both drug-resistant cells were divided into four groups: blank, emodin, gemcitabine, and emodin+gemcitabine. Cell viability was detected by MTT assay. Flow cytometry was performed to detect cell apoptosis rate and P-gp function. Quantitative real-time polymerase chain reaction and Western blotting were used to detect Survivin, XIAP, Caspase-9/3, NF-κB p65, IKKβ and IκB-α mRNA/ protein expressions, respectively. Electrophoretic mobility shift assay (EMSA) was performed to detect NF-κB binding activity. Rhodamine 123 efflux assay was used to detect P-gp function. Results: Emodin could inhibit cell activity in all cell lines. Both emodin and gemcitabine can significantly increase the apoptosis rate, and the combination of the two drugs can further significantly increase the apoptosis rate in normal pancreatic cancer cell lines. In both drugresistant pancreatic cancer cell lines, it can be observed that although gemcitabine can increase the apoptosis rate, the effect of promoting apoptosis is significantly lower than that of emodin; the drug combination can still significantly increase the apoptosis rate on the basis of emodin alone. Emodin can significantly reduce the mRNA and protein expression levels of Survivin, XIAP, NF-κB, and IKKβ, and significantly increase the mRNA and protein expression levels of Caspase-3/9 and IκB-α. Emodin significantly reduced NF-κB activity and emodin significantly promoted P-gp fluorescence intensity from Rhodamine 123 efflux assay. Conclusion: Emodin inhibits the expression of IKKβ, thereby inhibiting the expression and activity of downstream NF-κB, and inhibits P-gp function at the same time, ultimately achieving the purpose of reversing the drug-resistance of pancreatic cancer cell lines.

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Bioactivities of EF24, a Novel Curcumin Analog: A Review

Cited by 65 publications

References 101 publications

The Curcumin Analogue, EF-24, Triggers p38 MAPK-Mediated Apoptotic Cell Death via Inducing PP2A-Modulated ERK Deactivation in Human Acute Myeloid Leukemia Cells

The Curcumin Analogue, EF-24, Triggers p38 MAPK-Mediated Apoptotic Cell Death via Inducing PP2A-Modulated ERK Deactivation in Human Acute Myeloid Leukemia Cells

Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging

<p>Emodin Reverses Gemcitabine Resistance of Pancreatic Cancer Cell Lines Through Inhibition of IKKβ/NF-κB Signaling Pathway</p>

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