Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II, and III purified from Turmeric powder

Chearwae, Wanida; Anuchapreeda, Songyot; Nandigama, Krishnamachary; Ambudkar, Suresh V.; Limtrakul, Pornngarm

doi:10.1016/j.bcp.2004.07.009

Cited by 215 publications

(172 citation statements)

References 29 publications

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“…We reported previously that Cur is a P-gp reversing agent, which reduces P-gp expression and function in KB-V1 cells in vitro (Anuchapreeda et al, 2002). Cur also enhances the sensitivity of many anti-cancer drugs, including vinblastine (Anuchapreeda et al, 2002;Chearwae et al, 2004;Limtrakul et al, 2004). The in vitro data (Figure 1) confirmed that Cur (5 and 7.5 μM) could enhance PTX sensitivity approximately 2.5-and 33.3-fold, respectively.…”

Section: Discussionsupporting

confidence: 60%

“…The multidrug resistant (KB-V1) and drug sensitive (KB-3-1) cervical carcinoma cell (Anuchapreeda et al, 2002;Chearwae et al, 2004) lines were generous gifts from Dr. Michael M. Gottesman (National Cancer Institute, Bethesda, MD). Both cell lines were cultured in DMEM with 10% FBS, 2 mM L-glutamine, 50 U/ mL penicillin, and 50 μg/mL streptomycin, and 1 μg/ mL of vinblastine was added only to the KB-V1 culture medium.…”

Section: Cell Culturesmentioning

confidence: 99%

“…The cells were maintained in a humidified incubator at 37°C with an atmosphere containing 5% CO 2 . The expression of P-gp in KB-V1 and KB-3-1 cells was confirmed by western blot analysis, as described previously (Chearwae et al, 2004;Limtrakul et al, 2004).…”

Section: Cell Culturesmentioning

confidence: 99%

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Curcumin-loaded PLGA Nanoparticles Conjugated with Anti-P-glycoprotein Antibody to Overcome Multidrug Resistance

Punfa

Suzuki²,

Pitchakarn³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Asian Pac J Cancer Prev, 15 (21), 9249-9258 IntroductionMultidrug resistance (MDR) is a major problem for the success of cancer chemotherapy and is closely associated with treatment failure in the most common forms of cancer, including lung, colon, breast, and cervical cancer (Chang, 2003). Overexpression of P-glycoprotein (P-gp), a 170-kDa plasma membrane transporter, has been identified as one of the major causes of drug resistance in several cancers. P-gp belongs to the superfamily of ATP-binding cassette (ABC) transporters (Chang, 2003) that act as an ATP-dependent efflux pump and has a broad substrate specificity that includes xenobiotics (Bain et al., 1997), etoposide (Burgio et al., 1998), doxorubicin (Shen et al., 2008), vinblastine (Cisternino et al., 2004, and paclitaxel (PTX) (Jang et al., 2001;Gallo et al., 2003). Increased expression of P-gp, the product of the human MDR1 gene, is a well-characterized mechanism used by cancer cells to avoid the cytotoxic action of anticancer drugs. Based on decreases in intracellular drug accumulation by P-gp,

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Section: Discussionsupporting

confidence: 60%

Section: Cell Culturesmentioning

confidence: 99%

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Curcumin-loaded PLGA Nanoparticles Conjugated with Anti-P-glycoprotein Antibody to Overcome Multidrug Resistance

Punfa

Suzuki²,

Pitchakarn³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…The ethanolic extract was filtered through Whatman filter paper and ethanol was removed by a rotary evaporator. Curcumin I, II, and III were further purified from the crude ethanolic extract as described earlier (26).…”

Section: Methodsmentioning

confidence: 99%

Modulation of the function of the multidrug resistance–linked ATP-binding cassette transporter ABCG2 by the cancer chemopreventive agent curcumin

Chearwae

Shukla

Limtrakul

et al. 2006

Molecular Cancer Therapeutics

111

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Curcumin (curcumin I), demethoxycurcumin (curcumin II), and bisdemethoxycurcumin (curcumin III) are the major forms of curcuminoids found in the turmeric powder, which exhibit anticancer, antioxidant, and anti-inflammatory activities. In this study, we evaluated the ability of purified curcuminoids to modulate the function of either the wild-type 482R or the mutant 482T ABCG2 transporter stably expressed in HEK293 cells and drug-selected MCF-7 FLV1000 and MCF-7 AdVp3000 cells. Curcuminoids inhibited the transport of mitoxantrone and pheophorbide a from ABCG2-expressing cells. However, both cytotoxicity and [ 3 H]curcumin I accumulation assays showed that curcuminoids are not transported by ABCG2. Nontoxic concentration of curcumin I, II, and III sensitized the ABCG2-expressing cells to mitoxantrone, topotecan, SN-38, and doxorubicin. This reversal was not due to reduced expression because ABCG2 protein levels were unaltered by treatment with 10 Mmol/L curcuminoids for 72 hours. Curcumin I, II, and III stimulated (2.4-to 3.3-fold) ABCG2-mediated ATP hydrolysis and the IC 50 s were in the range of 7.5 to 18 nmol/L, suggesting a high affinity of curcuminoids for ABCG2. Curcuminoids also inhibited the photolabeling of ABCG2 with P]8-azidoATP to ABCG2, suggesting that they do not interact with the ATP-binding site of the transporter. Collectively, these data show that, among curcuminoids, curcumin I is the most potent modulator of ABCG2 and thus should be considered as a treatment to increase the efficacy of conventional chemotherapeutic drugs.

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“…Briefly, crude membranes from MCF-7 FLV1000 cells were prepared as described elsewhere (36). The crude membranes (1 mg protein/mL) were incubated with 20 Amol/L of the PKIs or 20 Amol/L fumitremorgin C for 10 min at room temperature in 50 mmol/L Tris-HCl (pH 7.5), to which 3 to 6 nmol/L [ 125 I]IAAP (2,200 Ci/mmol) was added and incubated for an additional 5 min under subdued light.…”

Section: Photo-cross-linking Of Abcg2 With [ 125 I]iaapmentioning

confidence: 99%

Inhibition of ABCG2-mediated transport by protein kinase inhibitors with a bisindolylmaleimide or indolocarbazole structure

Robey

Shukla

Steadman³

et al. 2007

Molecular Cancer Therapeutics

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ABCG2 is a transporter with potential importance in cancer drug resistance, drug oral absorption, and stem cell biology. In an effort to identify novel inhibitors of ABCG2, we examined the ability of commercially available bisindolylmaleimides (BIM) and indolocarbazole protein kinase inhibitors (PKI) to inhibit ABCG2, given the previous demonstration that the indolocarbazole PKI UCN-01 interacted with the transporter. At a concentration of 10 Mmol/L, all of the compounds tested increased intracellular fluorescence of the ABCG2-specific substrate pheophorbide a in ABCG2-transfected HEK-293 cells by 1.3-to 6-fold as measured by flow cytometry; the ABCG2-specific inhibitor fumitremorgin C increased intracellular fluorescence by 6.6-fold. In 4-day cytotoxicity assays, wild-type ABCG2-transfected cells were not more than 2-fold resistant to any of the compounds, suggesting that the PKIs are not significantly transported by ABCG2. BIMs I, II, III, IV, and V, K252c, and arcyriaflavin A were also able to inhibit [ 125 I]iodoarylazidoprazosin labeling of ABCG2 by 65% to 80% at 20 Mmol/L, compared with a 50% to 70% reduction by 20 Mmol/L fumitremorgin C. K252c and arcyriaflavin A were the most potent compounds, with IC 50 values for inhibition of [ 125 I]iodoarylazidoprazosin labeling of 0.37 and 0.23 Mmol/L, respectively. K252c and arcyriaflavin A did not have any effect on the ATPase activity of ABCG2. Four minimally toxic compounds-BIM IV, BIM V, arcyriaflavin A, and K252c-reduced the relative resistance of ABCG2-transfected cells to SN-38 in cytotoxicity assays. We find that indolocarbazole and BIM PKIs directly interact with the ABCG2 protein and may thus increase oral bioavailability of ABCG2 substrates.

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Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II, and III purified from Turmeric powder

Cited by 215 publications

References 29 publications

Curcumin-loaded PLGA Nanoparticles Conjugated with Anti-P-glycoprotein Antibody to Overcome Multidrug Resistance

Curcumin-loaded PLGA Nanoparticles Conjugated with Anti-P-glycoprotein Antibody to Overcome Multidrug Resistance

Modulation of the function of the multidrug resistance–linked ATP-binding cassette transporter ABCG2 by the cancer chemopreventive agent curcumin

Inhibition of ABCG2-mediated transport by protein kinase inhibitors with a bisindolylmaleimide or indolocarbazole structure

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