Tetrandrine enhances glucocorticoid receptor translocation possibly via inhibition of P-glycoprotein in daunorubicin-resistant human T lymphoblastoid leukemia cells

Xu, Wen‐Cheng; Wang, Xiaoqin; Chen, Shuhe; Wu, Huijun; Tanaka, Sachiko; Onda, Kenji; Sugiyama, Kentaro; Yamada, Hideaki; Hirano, Toshihiko

doi:10.1016/j.ejphar.2020.173232

Cited by 13 publications

(16 citation statements)

References 29 publications

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“…The IC 50 values of MP were determined using GraphPad Prism 8 [ 16 , 17 ]. The combination index was calculated using CompuSyn software, and a combination index < 1, 1, and > 1 represents synergistic, additive, and antagonistic effects, respectively [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…MOLT-4 cells, which express low levels of P-glycoprotein, were purchased from DS Pharma Biomedical Co., Ltd. (Osaka, Japan). MOLT-4/DNR cells, which are known to express large amounts of P-glycoprotein, were developed from the MOLT-4 cell line in our laboratory by exposing the parent cells to increasing concentrations of daunorubicin (DNR) over 3 months [ 18 ]. The expression of functional P-glycoprotein in these two cell lines was identified in our previous study [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…MOLT-4/DNR cells, which are known to express large amounts of P-glycoprotein, were developed from the MOLT-4 cell line in our laboratory by exposing the parent cells to increasing concentrations of daunorubicin (DNR) over 3 months [ 18 ]. The expression of functional P-glycoprotein in these two cell lines was identified in our previous study [ 18 ]. MOLT-4 and MOLT-4/DNR cells were maintained in RPMI 1640 medium containing 10% FBS, 1000,000 IU/L penicillin, and 100 mg/L streptomycin [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

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Cepharanthine synergistically promotes methylprednisolone pharmacodynamics against human peripheral blood mononuclear cells possibly via regulation of P-glycoprotein/glucocorticoid receptor translocation

Xu,

Chen,

Wang

et al. 2024

BMC Complement Med Ther

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Background Cepharanthin® alone or in combination with glucocorticoid (GC) has been used to treat chronic immune thrombocytopenia (ITP) since the 1990s. Cepharanthine (CEP) is one of the main active components of Cepharanthin®. The purpose of this study was to investigate the effects of CEP on GC pharmacodynamics on immune cells and analyse the possible action mechanism of their interactions. Methods Peripheral blood mononuclear cells (PBMCs), T lymphocytic leukemia MOLT-4 cells and daunorubicin resistant MOLT-4 cells (MOLT-4/DNR) were used to evaluate the pharmacodynamics and molecular mechanisms. Drug pharmacodynamics was evaluated by WST-8 assay. P-glycoprotein function was examined by rhodamine 123 assay. CD4+CD25+Foxp3+ regulatory T cells and Th1/Th2/Th17 cytokines were detected by flow cytometry. P-glycoprotein expression and GC receptor translocation were examined by Western blot. Results CEP synergistically increased methylprednisolone (MP) efficacy with the suppressive effect on the cell viability of PBMCs. 0.3 and 1 μM of CEP significantly inhibited P-glycoprotein efflux function of CD4+ cells, CD8+ cells, and lymphocytes (P<0.05). 0.03~3 μM of CEP also inhibited the P-glycoprotein efflux function in MOLT-4/DNR cells in a concentration-dependent manner (P<0.001). However, 0.03~3 μM of CEP did not influence P-glycoprotein expression. 0.03~0.3 μM of CEP significantly increased the GC receptor distribution from the cytoplasm to the nucleus in a concentration-dependent manner in MOLT-4/DNR cells. The combination did not influence the frequency of CD4+, CD4+CD25+ and CD4+CD25+Foxp3+ T cells or the secretion of Th1/Th2/Th17 cytokines from PBMCs. In contrast, CEP alone at 1 μM decreased the percentage of CD4+ T cell significantly (P<0.01). It also inhibited the secretion of IL-6, IL-10, IL-17, TNF-α, and IFN-γ. Conclusions CEP synergistically promoted MP pharmacodynamics to decrease the cell viability of the mitogen-activated PBMCs, possibly via inhibiting P-glycoprotein function and potentiating GC receptor translocation. The present study provides new evidence of the therapeutic effect of Cepharanthin® alone or in combination with GC for the management of chronic ITP.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cepharanthine synergistically promotes methylprednisolone pharmacodynamics against human peripheral blood mononuclear cells possibly via regulation of P-glycoprotein/glucocorticoid receptor translocation

Xu,

Chen,

Wang

et al. 2024

BMC Complement Med Ther

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“…Interestingly, these homodimers, as well as dimers of abacavir, were designed to also revert to the monomeric drug within the reducing environment of the cell, thus acting as both ABC transporter inhibitors and prodrugs [84,146] . Recently, homodimers of triazole-bridged flavonoids were also shown to Fourth generation Natural product derivatives: Flavonoids (Curcumin * [163] , Apigenin * [164] ), Polyphenols (Quercetin * [165] , Resveratrol *, † [166] ), Antimalarials (Chloroquine *, † [167] ), Alkaloids (Galegine *[168] , Nitensidine A * [169] ), Fungal (Ko143 † [170] , Tryprostatin A † [171] ), Chinese herbal medicines (Artemisinin * [172] , Tetrandrine * [173] ), Marine (Kendarimide* A, Sipholenol A*) [174] Repurposing FDA-approved drugs [175] : Imatinib* , † , Vardenafil*, Azithromycin* , † , Chlorpromazine* , †…”

Section: Inhibitor Design and Evaluationmentioning

confidence: 99%

The roles of the human ATP-binding cassette transporters P-glycoprotein and ABCG2 in multidrug resistance in cancer and at endogenous sites: future opportunities for structure-based drug design of inhibitors

Goebel¹,

Chmielewski²,

Hrycyna³

2021

CDR

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“…Tetrandrine isolated from Stephania tetrandra S. Moore , is involved in downregulating the expression of P‐glycoprotein and effectively regulates translocation of the nuclear glucocorticoid receptor in MOLT‐4T cells (W. Xu et al, 2020). In addition, a study reported the immunomodulatory property of Azhadirachta indica (neem) crude extract and fraction in Balb/c mice (Beuth, Schneider, & Ko, 2006).…”

Section: Plants As Biological Sources For Immunomodulatorsmentioning

confidence: 99%

Potential therapeutic applications of phytoconstituents as immunomodulators: Pre‐clinical and clinical evidences

Ali

Singh

Datusalia

2021

Phytotherapy Research

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Autoimmune and infectious diseases are the major public health issues and have gained great attention in the last few years for the search of new agents with therapeutic benefits on the host immune functions. In recent years, natural products (NPs) have been studied broadly for their multi-targeted activities under pathological conditions. Interestingly, several attempts have been made to outline the immunomodulatory properties of NPs. Research on in-vitro and in-vivo models have shown the immunomodulatory activity of NPs, is due to their antiinflammatory property, induction of phagocytosis and immune cells stimulation activity. Moreover, studies on humans have suggested that phytomedicines reduce inflammation and could provide appropriate benefits either in single form or complex combinations with other agents preventing disease progression, subsequently enhancing the efficacy of treatment to combat multiple malignancies.However, the exact mechanism of immunomodulation is far from clear, warranting more detailed investigations on their effectiveness. Nevertheless, the reduction of inflammatory cascades is considered as a prime protective mechanism in a number of inflammation regulated autoimmune diseases. Altogether, this review will discuss the biological activities of plant-derived secondary metabolites, such as polyphenols, alkaloids, saponins, polysaccharides and so forth, against various diseases and their potential use as an immunomodulatory agent under pathological conditions.

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Tetrandrine enhances glucocorticoid receptor translocation possibly via inhibition of P-glycoprotein in daunorubicin-resistant human T lymphoblastoid leukemia cells

Cited by 13 publications

References 29 publications

Cepharanthine synergistically promotes methylprednisolone pharmacodynamics against human peripheral blood mononuclear cells possibly via regulation of P-glycoprotein/glucocorticoid receptor translocation

Cepharanthine synergistically promotes methylprednisolone pharmacodynamics against human peripheral blood mononuclear cells possibly via regulation of P-glycoprotein/glucocorticoid receptor translocation

The roles of the human ATP-binding cassette transporters P-glycoprotein and ABCG2 in multidrug resistance in cancer and at endogenous sites: future opportunities for structure-based drug design of inhibitors

Potential therapeutic applications of phytoconstituents as immunomodulators: Pre‐clinical and clinical evidences

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