A Combination of Curcumin with Either Gramicidin or Ouabain Selectively Kills Cells That Express the Multidrug Resistance-linked ABCG2 Transporter

Rao, Divya; Liu, Haiyan; Ambudkar, Suresh V.; Mayer, Michael

doi:10.1074/jbc.m114.576819

Cited by 28 publications

(19 citation statements)

References 50 publications

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“…In addition, curcumin also could inhibit the expression of MRP1 in a concentration dependent manner in Y79 cells . Besides, it was reported that curcumin inhibited drug efflux and increased the efficacy of many anticancer agents in multidrug‐resistant cancers . Moreover, curcumin and demethoxycurcumin could inhibit P‐gp but BDMC may modulate the function of other efflux transporters such as MRPs .…”

Section: Discussionmentioning

confidence: 99%

Efflux excretion of bisdemethoxycurcumin‐O‐glucuronide in UGT1A1‐overexpressing HeLa cells: Identification of breast cancer resistance protein (BCRP) and multidrug resistance‐associated proteins 1 (MRP1) as the glucuronide transporters

et al. 2018

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Bisdemethoxycurcumin (BDMC) was a natural curcuminoid with many bioactivities present in turmeric (Curcuma longa L.). However, the disposition mechanisms of BDMC via uridine 5 0 -diphospho-glucuronosyltransferase (UGT) metabolism still remain unclear. Therefore, we aimed to determine the potential efflux transporters for the excretion of BDMC-O-glucuronide. Herein, chemical inhibition assays (Ko143, MK571, dipyridamole, and leukotriene C4) and biological inhibition experiments including stable knocked-down of breast cancer resistance protein (BCRP), multidrug resistance-associated proteins (MRPs) transporters were both performed in a HeLa cell line stably overexpressing UGT1A1 established previously. The results indicated that Ko143 (5 and 20 μM) caused a marked reduction in excretion rate (18.4-55.6%) and elevation of intracellular BDMC-O-glucuronide (28.8-48.1%), whereas MK-571 (5 and 20 μM) resulted in a significant decrease in excretion rate (6.2-61.6%) and increase of intracellular BDMC-O-glucuronide (maximal 27.1-32.6%). Furthermore, shRNAmediated silencing of BCRP transporter led to a marked reduction in the excretion rate (21.1-36.9%) and an obvious elevation of intracellular glucuronide (24.9%). Similar results were observed when MRP1 was partially silenced. In addition, MRP3 and MRP4 silencing both displayed no obvious changes on the excretion rate and intracellular levels of glucuronide. In conclusion, chemical inhibition and gene silencing results both indicated that generated BDMC-O-glucoside were excreted primarily by the BCRP and MRP1 transporters.

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Section: Discussionmentioning

confidence: 99%

Efflux excretion of bisdemethoxycurcumin‐O‐glucuronide in UGT1A1‐overexpressing HeLa cells: Identification of breast cancer resistance protein (BCRP) and multidrug resistance‐associated proteins 1 (MRP1) as the glucuronide transporters

et al. 2018

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“…The MTT-bioassay data unambiguously showed that the pH-sensitive liposomal formulation of curcumin proved to significantly outclass the free drug in terms of The established high efficacy of formulated curcumin in resistant cells is of special interest, since this compound has been shown to restore the responsiveness to anticancer drugs and is considered as a potential multidrug-resistance reversal agent (Li et al, 2013;Li et al, 2011;Misra and Sahoo, 2011;Rao et al, 2014;Roy and Mukherjee, 2014;Sreekanth et al, 2011;Sreenivasan et al, 2012). The apoptosis assay firmly demonstrated that liposomal curcumin is a potent inducer of apoptotic DNA-fragmentation in HL-60, in compliance to preceding reports (Alaikov et al, 2007;Liao et al, 2008;Tan et al, 2006) and especially in HL-60/CDDP cells which proved to be more sensitive to the apoptogenic effects of equieffective levels of curcumin.…”

Section: Discussionmentioning

confidence: 96%

Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems

Jelezova

Drakalska

Momekova

et al. 2015

European Journal of Pharmaceutical Sciences

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Curcumin is a perspective drug candidate with pleiotropic antineoplastic activity, whose exceptionally low aqueous solubility and poor pharmacokinetic properties have hampered its development beyond the preclinical level. A possible approach to overcome these limitations is the encapsulation of curcumin into nano-carriers, incl. liposomes. The present contribution is focused on feasibility of using hybrid pH-sensitive liposomes, whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with PEGylated tertbutylcalix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. The inclusion complexes were encapsulated in dipalmithoylphosphathydilcholine:cholesterol liposomes, whose membranes were grafted with a poly(isoprene-b-acrylic acid) diblock copolymer to confer pH-sensitivity. The liposomes were characterized by DLS, ζ-potential measurements, cryo-TEM, curcumin encapsulation efficacy, loading capacity, and in vitro release as a function of pH. Free and formulated curcumin were further investigated for cytotoxicity, apoptosis-induction and caspase-8, and 9 activation in chemosensitive HL-60 and its resistant sublines HL-60/Dox and HL-60/CDDP. Formulated curcumin was superior cytotoxic and apoptogenic agent vs. the free drug. The mechanistic assay demonstrated that the potent proapoptotic effects of pH-sensitive liposomal curcumin presumably mediated via recruitment of both extrinsic and intrinsic apoptotic pathways in both HL-60 and HL-60/CDDP cells.

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“…The discovery of MRP1 indicates the finding of other homologs of ABC family transporters such as the other eight ABCC subfamilies, six of which have been confirmed to be involved in the exclusion of anticancer agents and antiviral compounds 19, 20. Besides P‐gp and MRP1, other MDR‐related membrane transporters (e.g., the breast cancer resistance protein BCRP, also known as ABCG2) are also important ABC transporter,21, 22, 23 which plays an essential role in resistance to a variety of cancer therapeutic agents, including mitoxantrone, topotecan, doxorubicin, and SN‐38 24. Moreover, other ABC family transporters have also been found to be associated with drug resistance, such as the “sister of P‐gp,” ABCB11, and ABCA2, although their roles in cancer multidrug resistance remain unclear 25, 26…”

Section: Mechanisms Of Cancer Multidrug Resistancementioning

confidence: 99%

Inorganic Nanocarriers Overcoming Multidrug Resistance for Cancer Theranostics

et al. 2016

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Cancer multidrug resistance (MDR) could lead to therapeutic failure of chemotherapy and radiotherapy, and has become one of the main obstacles to successful cancer treatment. Some advanced drug delivery platforms, such as inorganic nanocarriers, demonstrate a high potential for cancer theranostic to overcome the cancer‐specific limitation of conventional low‐molecular‐weight anticancer agents and imaging probes. Specifically, it could achieve synergetic therapeutic effects, demonstrating stronger killing effects to MDR cancer cells by combining the inorganic nanocarriers with other treatment manners, such as RNA interference and thermal therapy. Moreover, the inorganic nanocarriers could provide imaging functions to help monitor treatment responses, e.g., drug resistance and therapeutic effects, as well as analyze the mechanism of MDR by molecular imaging modalities. In this review, the mechanisms involved in cancer MDR and recent advances of applying inorganic nanocarriers for MDR cancer imaging and therapy are summarized. The inorganic nanocarriers may circumvent cancer MDR for effective therapy and provide a way to track the therapeutic processes for real‐time molecular imaging, demonstrating high performance in studying the interaction of nanocarriers and MDR cancer cells/tissues in laboratory study and further shedding light on elaborate design of nanocarriers that could overcome MDR for clinical translation.

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A Combination of Curcumin with Either Gramicidin or Ouabain Selectively Kills Cells That Express the Multidrug Resistance-linked ABCG2 Transporter

Cited by 28 publications

References 50 publications

Efflux excretion of bisdemethoxycurcumin‐O‐glucuronide in UGT1A1‐overexpressing HeLa cells: Identification of breast cancer resistance protein (BCRP) and multidrug resistance‐associated proteins 1 (MRP1) as the glucuronide transporters

Efflux excretion of bisdemethoxycurcumin‐O‐glucuronide in UGT1A1‐overexpressing HeLa cells: Identification of breast cancer resistance protein (BCRP) and multidrug resistance‐associated proteins 1 (MRP1) as the glucuronide transporters

Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems

Inorganic Nanocarriers Overcoming Multidrug Resistance for Cancer Theranostics

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