Demethoxycurcumin Modulates Human P-Glycoprotein Function via Uncompetitive Inhibition of ATPase Hydrolysis Activity

Teng, Yu‐Ning; Hsieh, Ying‐Hen; Hung, Chin‐Chuan; Lin, Hui‐Yi

doi:10.1021/jf5042307

Cited by 32 publications

(29 citation statements)

References 33 publications

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“…This strategy could be used to reverse multidrug resistance against select cancers. In a study by Teng, Hsieh, Hung, and Lin (2015) it was shown that DMC inhibited P-gp (Table 1)…”

Section: Dmc As a Chemosensitizing Agentmentioning

confidence: 99%

Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties

Hatamipour

Ramezani

Tabassi

et al. 2018

Journal Cellular Physiology

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The eradication of cancer in a patient remains an elusive challenge despite advances in early detection and diagnosis, chemo- and immunotherapy, pinpoint radiation treatments, and expert surgical intervention. Although significant gains have been made in our understanding of cancer cell biology, a definite cure for most cancers does not exist at present. Thus, it is not surprising that the research and medical communities continue to explore the importance and therapeutic potential of natural products in their multimodality cancer treatment approach. Curcuminoids found in turmeric are one such class of natural products that have been extensively investigated for their potential to halt the progression of cancer cell proliferation and, more important, to stop metastasis from occurring. In this review, we examine one curcuminoid (demethoxycurcumin [DMC]) largely because of its increased stability and better aqueous solubility at physiological pH, unlike the more well-known curcuminoid (curcumin), which is largely unabsorbed after oral ingestion. The present review will focus on the signaling pathways that DMC utilizes to modulate the growth, invasion, and metastasis of cancer cells in an effort to provide enhanced mechanistic insight into DMC's action as it pertains to brain, ovarian, breast, lung, skin, and prostate cancer. Additionally, this review will attempt to provide an overview of DMC's mechanism of action by modulating apoptosis, cell cycle, angiogenesis, metastasis, and chemosensitivity. Lastly, it is hoped that increased understanding will be gained concerning DMC's interactive role with microRNA-551a, 5' adenosine monophosphate-activated protein kinase, nuclear factor-κB, Wnt inhibitory factor-1, and heat shock protein 70 to affect the progression of cancer.

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“…This strategy could be used to reverse multidrug resistance against select cancers. In a study by Teng, Hsieh, Hung, and Lin (2015) it was shown that DMC inhibited P-gp (Table 1)…”

Section: Dmc As a Chemosensitizing Agentmentioning

confidence: 99%

Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties

Hatamipour

Ramezani

Tabassi

et al. 2018

Journal Cellular Physiology

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“…The method has been described in our previous research [9]. The calcein fluorescence generated within the cells was detected by BioTek Synergy HT Multi-Mode Microplate Reader using excitation wavelength 485 nm and emission wavelength 528 nm at 37 • C temperature every 3 min for 30 min.…”

Section: Intracellular Calcein Accumulation Assaymentioning

confidence: 99%

“…The method has been described in our previous research [9]. The relative ABCB1 mRNA expression levels were normalized to the amount of GAPDH in the same cDNA and evaluated by StepOnePlus TM Real-Time PCR System (Applied Biosystems ® , Waltham, MA, USA).…”

Section: Real-time Quantitative Rt-pcrmentioning

confidence: 99%

“…The method has been described in our previous research [9]. The conformation change of P-gp after the addition of ZA-A, ZA-B or ZA-C was examined by using a MDR1 Shift Assay kit (EMD Millipore Corp., Billerica, MA, USA) according to the manufacturer's protocol.…”

Section: Mdr1 Shift Assaymentioning

confidence: 99%

“…Resources are abundant in nature, including in plants, fungi and marine organisms. Curcuminoids are well-known P-gp inhibitors from plants, and nanotechnological pharmaceutical development and chemical modification are underway to improve the effects of these promising candidates [9]. Regarding fungi, a study demonstrated that crude ethanol extracts from Antrodia cinnamomea fruiting bodies are potent P-gp inhibitors [10].…”

Section: Introductionmentioning

confidence: 99%

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Zhankuic Acids A, B and C from Taiwanofungus camphoratus Act as Cytotoxicity Enhancers by Regulating P-Glycoprotein in Multi-Drug Resistant Cancer Cells

Teng

Wang

et al. 2019

Biomolecules

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Since P-glycoprotein (P-gp)-related multidrug resistance (MDR) remains the most important unsolved problem in cancer treatment, scientists are attempting to find potential structures from natural resources. The aim of the present study was to elucidate whether the triterpenoids from Taiwanofungus camphoratus could reverse cancer MDR by influencing P-gp efflux pump. Substrates efflux assay and P-gp ATPase activity assay were conducted to reveal the molecular mechanisms of P-gp inhibition, while SRB assay, cell cycle analyses and apoptosis analyses were performed to confirm the cancer MDR modulating effects. The results indicated that Zhankuic acids A, B and C (ZA-A, ZA-B and ZA-C) impacted P-gp efflux function in competitive, noncompetitive and competitive manners, respectively. Furthermore, these triterpenoids all demonstrated inhibitory patterns on both basal P-gp ATPase activity and verapamil-stimulated ATPase activity. In terms of MDR reversal effects, ZA-A sensitized the P-gp over-expressing cell line (ABCB1/Flp-In TM -293) and MDR cancer cell line (KB/VIN) toward clinically used chemotherapeutic drugs, including doxorubicin, paclitaxel and vincristine, exhibiting the best cytotoxicity enhancing ability among investigated triterpenoids. The present study demonstrated that ZA-A, ZA-B and ZA-C, popular triterpenoids from T. camphoratus, effectively modulated the drug efflux transporter P-gp and reversed the cancer MDR issue.

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Demethoxycurcumin induces apoptosis in HER2 overexpressing bladder cancer cells through degradation of HER2 and inhibiting the PI3K/Akt pathway

Kao

Cheng

Yang

et al. 2021

Environmental Toxicology

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Bladder cancer is the most common malignancy of the urinary tract and arising from the epithelial lining of the urinary bladder. Resistance to cytotoxic therapies is associated with overexpression of oncogenic proteins; including HER2, and Akt in chemotherapy resistance of bladder cancer. Various studies demonstrated that curcuminoids, the most important active phenolic compounds of turmeric (Curcuma longa), have anti‐tumor activities in a wide range of human malignant cell lines. The aim of this study is to evaluate whether curcuminoids (curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin) could repress the expression of HER2 in HER2‐overexpressing bladder cancer cells. Among the test compounds, DMC significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2‐overexpressing bladder cancer cells. DMC decreases HER2 level through inhibiting the interaction of HER2 and Hsp90. Our study also indicated that DMC showed additive activity in combination with chemotherapeutic agents, including paclitaxel and cisplatin. These findings show that DMC should be developed further as a new antitumor drug candidate for treatment of HER2‐overexpressing bladder cancer.

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Demethoxycurcumin Modulates Human P-Glycoprotein Function via Uncompetitive Inhibition of ATPase Hydrolysis Activity

Cited by 32 publications

References 33 publications

Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties

Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties

Zhankuic Acids A, B and C from Taiwanofungus camphoratus Act as Cytotoxicity Enhancers by Regulating P-Glycoprotein in Multi-Drug Resistant Cancer Cells

Demethoxycurcumin induces apoptosis in HER2 overexpressing bladder cancer cells through degradation of HER2 and inhibiting the PI3K/Akt pathway

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