Stemona alkaloids, from traditional Thai medicine, increase chemosensitivity via P-glycoprotein-mediated multidrug resistance

Chanmahasathien, Wisinee; Ampasavate, Chadarat; Greger, Harald; Limtrakul, Pornngarm

doi:10.1016/j.phymed.2010.07.014

Cited by 55 publications

(46 citation statements)

References 17 publications

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“…15) In our previous study, Stemona alkaloids including stemofoline from Stemona burkillii, stemocurtisine and oxystemocurrine from Stemona aphylla have been isolated and evaluated for synergistic growth inhibitory effect with cancer chemotherapeutic agents. 16) We found that stemofoline had the ability to reverse the MDR phenotype, increased the intracellular accumulation of P-gp fluorescent substrates, decreased the [ 3 H]-vinblastine efflux in multidrugresistant human cervical carcinoma KB-V1 cells and increased their sensitivity to vinblastine, paclitaxel and doxorubicin. 12,16) In this study, twelve stemofoline derivatives were prepared Regular Article * To whom correspondence should be addressed.…”

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confidence: 81%

“…16) We found that stemofoline had the ability to reverse the MDR phenotype, increased the intracellular accumulation of P-gp fluorescent substrates, decreased the [ 3 H]-vinblastine efflux in multidrugresistant human cervical carcinoma KB-V1 cells and increased their sensitivity to vinblastine, paclitaxel and doxorubicin. 12,16) In this study, twelve stemofoline derivatives were prepared Regular Article * To whom correspondence should be addressed. e-mail: plimtrak@med.cmu.ac.th…”

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confidence: 81%

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Inhibition of P-Glycoprotein Mediated Multidrug Resistance by Stemofoline Derivatives

Umsumarng

Pintha

Pitchakarn

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATPbinding cassette (ABC) drug transporters including P-glycoprotein (P-gp) that actively efflux chemotherapeutic drugs from cancer cells. We examined the mutidrug resistance reversing property of stemofoline derivatives in drug-resistance human cervical carcinoma (KB-V1) and human leukemic (K562/Adr) cell lines that overexpress P-gp. Didehydrostemofoline and eleven of its derivatives were synthesized and the cytotoxicity and their effect on doxorubicin, vinblastine and paclitaxel sensitivity in drug resistant (KB-V1 and K562/ Adr) and drug sensitive (KB-3-1 and K562) cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were determined. We found that three out of the twelve stemofoline derivatives including OH-A1, NH-B6 and NH-D6 showed commitment efficiency to increase sensitivity to doxorubicin, vinblastine and paclitaxel in KB-V1 cells and increase sensitivity to doxorubicin, and paclitaxel in K562/Adr cells whereas the effects have not been seen in their parental sensitive cancer cell lines (KB-3-1 and K562). These results indicate that stemofoline derivatives reversed P-gp-mediated multidrug resistance in vitro, and thus could be developed as effective chemosensitizers to treat multidrug-resistant cancers. The molecular mechanism of modulation of P-gp would be further determined.

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confidence: 81%

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confidence: 81%

Inhibition of P-Glycoprotein Mediated Multidrug Resistance by Stemofoline Derivatives

Umsumarng

Pintha

Pitchakarn

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Many pharmacologic agents from diverse structure classes have been identified as MDR modulators. It has been reported that many agents from natural products and dietary plants also modulate MDR phenotype of cancer cells including the extraction from Rosmarinus officinalis, Momordica charantia [4,5] , Stemona aphylla [6] , and including Curcuma longa [7,8] . Curcumin (Cur), a phenolic compound purified from the rhizome of Curcuma longa, has a long history of being used as a spice and in traditional medicine.…”

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confidence: 99%

Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer cells

et al. 2012

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Aim:To compare the anti-cancer activity and cellular uptake of curcumin (Cur) delivered by targeted and non-targeted drug delivery systems in multidrug-resistant cervical cancer cells. Methods: Cur was entrapped into poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Cur-NPs) in the presence of modified-pluronic F127 stabilizer using nano-precipitation technique. On the surface of Cur-NPs, the carboxy-terminal of modified pluronic F127 was conjugated to the amino-terminal of anti-P-glycoprotein (P-gp) (Cur-NPs-APgp). The physical properties of the Cur-NPs, including particle size, zeta potential, particle morphology and Cur release kinetics, were investigated. Cellular uptake and specificity of the Cur-NPs and Cur-NPs-APgp were detected in cervical cancer cell lines KB-V1 (higher expression of P-gp) and KB-3-1 (lower expression of P-gp) using fluorescence microscope and flow cytometry, respectively. Cytotoxicity of the Cur-NPs and Cur-NPs-APgp was determined using MTT assay. Results: The particle size of Cur-NPs and Cur-NPs-APgp was 127 and 132 nm, respectively. The entrapment efficiency and actual loading of Cur-NPs-APgp (60% and 5 µg Cur/mg NP) were lower than those of Cur-NPs (99% and 7 µg Cur/mg NP). The specific binding of Cur-NPs-APgp to KB-V1 cells was significantly higher than that to KB-3-1 cells. Cellular uptake of Cur-NPs-APgp into KB-V1 cells was higher, as compared to KB-3-1 cells. However, the cellular uptake of Cur-NPs and Cur-NPs-IgG did not differ between the two types of cells. Besides, the cytotoxicity of Cur-NPs-APgp in KB-V1 cells was higher than those of Cur and Cur-NPs. Conclusion:The results demonstrate that Cur-NPs-APgp targeted to P-gp on the cell surface membrane of KB-V1 cells, thus enhancing the cellular uptake and cytotoxicity of Cur.

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“…They were unable to inhibit KB-V1 cells growth when vinblastine, PB or PC were administered as single agents, but when co-administered with vinblastine, these compounds showed inhibition of up to 77.7%. Equimolar dose of verapamil when tested was less effective 98 . These suggest that PB and PC are potential inhibitors of P-gp.…”

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confidence: 88%

Advances in plant-based inhibitors of P-glycoprotein

Zhou

James

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Multidrug resistance (MDR) has emerged as the main problem in anti-cancer therapy. Although MDR involves complex factors and processes, the main pivot is the expression of multidrug efflux pumps. P-glycoprotein (P-gp) belongs to the family of adenosine triphosphate (ATP)-binding cassette (ABC) transporters. It functions in cellular detoxification, pumping a wide range of xenobiotic compounds out of the cell. An attractive therapeutic strategy for overcoming MDR is to inhibit the transport function of P-gp and thus, increase intracellular concentration of drugs. Recently, various types of P-gp inhibitors have been found and used in experiments. However, none of them has passed clinical trials due to their high side-effects. Hence, the search for alternatives, such as plant-based P-gp inhibitors have gained attention recently. Therefore, we give an overview of the source, function, structure and mechanism of plant-based P-gp inhibitors and give more attention to cancer-related studies. These products could be the future potential drug candidates for further research as P-gp inhibitors.

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Stemona alkaloids, from traditional Thai medicine, increase chemosensitivity via P-glycoprotein-mediated multidrug resistance

Cited by 55 publications

References 17 publications

Inhibition of P-Glycoprotein Mediated Multidrug Resistance by Stemofoline Derivatives

Inhibition of P-Glycoprotein Mediated Multidrug Resistance by Stemofoline Derivatives

Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer cells

Advances in plant-based inhibitors of P-glycoprotein

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