Kenneth K W To

The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Publications (61)287.81 Total impact

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    ABSTRACT: The objective of this study was to fabricate dasatinib-loaded nanoparticles and evaluate their efficacy in inhibiting cellular processes of the retinal pigment epithelium (RPE) related to proliferative vitreoretinopathy (PVR), for which there are no approved pharmacological approaches. We successfully encapsulated dasatinib, a poorly soluble multi-targeted tyrosine kinase inhibitor which has great potential for the treatment of PVR, into nanoparticles prepared from micellation of PEG-b-PCL. The size of the nanomicelles was approximately 55nm with a narrow distribution. They increased the solubility of dasatinib by 475× and provided a sustained drug release. ARPE-19, an immortal RPE cell line, was used to assess the in vitro efficacy of micellar dasatinib because the RPE is believed to play a key role in the pathogenesis of PVR. Three cell-based assays, namely, proliferation, adhesion and migration, which represent three important PVR-related cellular changes of the RPE, were conducted and the cytotoxicity of micelles was also evaluated. Both blank and dasatinib-loaded micelles were non-cytotoxic towards ARPE-19 cells. Micellar dasatinib significantly inhibited cell proliferation, adhesion and migration compared to the free drug; this might be attributable to enhanced solubility. PEG-b-PCL micelles were taken up into the ARPE-19 cells by an energy-dependent clatharin and caveolae-mediated endocytosis. Our results indicated that cellular uptake and the anti-proliferation effect of drugloaded micelles were linearly correlated. Drug loading appears to be a critical parameter for cellular uptake which in turn impacts the in vitro bioactivities of polymeric micelles. Our results clearly demonstrated that dasatinib-encapsulated micelles offer considerable promise in the management of PVR.
    No preview · Article · Jan 2016 · Colloids and surfaces B: Biointerfaces
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    Jing Hu · Xu Zhang · Fang Wang · Xiaokun Wang · Ke Yang · Meng Xu · Kenneth K W To · Qingshan Li · Liwu Fu
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    ABSTRACT: Multidrug resistance (MDR) is the leading cause of treatment failure in cancer chemotherapy. The overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, ABCC1 and ABCG2, play a key role in mediating MDR by pumping anticancer drugs out from cancer cells. Ceritinib (LDK378) is a second-generation tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) currently in phase III clinical trial for the treatment of non-small cell lung cancer. Here, we found that ceritinib remarkably enhanced the efficacy of chemotherapeutic drugs in ABCB1 or ABCG2 over-expressing cancer cells in vitro and in vivo. Ceritinib significantly increased the intracellular accumulation of chemotherapeutic agents such as doxorubicin (DOX) by inhibiting ABCB1 or ABCG2-mediated drug efflux in the transporters-overexpressing cells. Mechanistically, ceritinib is likely a competitive inhibitor of ABCB1 and ABCG2 because it competed with [125I]-iodoarylazidoprazosin for photo affinity labeling of the transporters. On the other hand, at the transporters-inhibiting concentrations, ceritinib did not alter the expression level of ABCB1 and ABCG2, and phosphorylation status of AKT and ERK1/2. Thus the findings advocate further clinical investigation of combination chemotherapy of ceritinib and other conventional chemotherapeutic drugs in chemo-refractory cancer patients.
    Preview · Article · Nov 2015 · Oncotarget
  • Yuming Wei · Kenneth K.W. To · Steve C.F. AU-Yeung
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    ABSTRACT: Imatinib, a multitargeted tyrosine kinase inhibitor, exhibits potent anticancer activity against leukemia harboring the Bcr-Abl oncogene and some solid tumors overexpressing c-kit and PDGFR. However, its clinical efficacy is severely compromised by the emergence of resistance primarily due to acquired mutations in the Bcr-Abl kinase domain. In this study, we showed that combination of imatinib with platinum (Pt)-based anticancer agents, including cisplatin and oxaliplatin, exhibited synergistic cytotoxic effect specifically in Bcr-Abl+ human chronic myeloid leukemia cell line K562 but not in Bcr-Abl− RPMI8226 cells. Importantly, the synergistic effect was also found to circumvent imatinib resistance in an imatinib-selected resistant subline K562 ima1.0. The combination treatment increased apoptosis and DNA damage. Mechanistic study revealed that increased inhibition of Bcr-Abl and downstream ERK phosphorylation by the drug combination may contribute to the synergistic effect.
    No preview · Article · Nov 2015 · Journal of Pharmacological Sciences
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    ABSTRACT: The overexpression of ATP-binding cassette (ABC) transporters is closely associated with the development of multidrug resistance (MDR) in certain types of cancer, which represents a formidable obstacle to the successful cancer chemotherapy. Here, we investigated that cetuximab, an EGFR monoclonal antibody, reversed the chemoresistance mediated by ABCB1, ABCG2 or ABCC1. Our results showed that cetuximab significantly enhanced the cytotoxicity of ABCB1 substrate agent in ABCB1-overexpressing MDR cells but had no effect in their parental drug sensitive cells and ABCC1, ABCG2 overexpressing cells. Furthermore, cetuximab markedly increased intracellular accumulation of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABCB1-overexpressing MDR cancer cells in a concentration-dependent manner. Cetuximab stimulated the ATPase activity but did not alter the expression level of ABCB1 or block phosphorylation of AKT and ERK. Interestingly, cetuximab decreased the cell membrane fluidity which was known to decrease the function of ABCB1. Our findings advocate further clinical investigation of combination chemotherapy of cetuximab and conventional chemotherapeutic drugs in ABCB1 overexpressing cancer patients.
    Preview · Article · Oct 2015 · Oncotarget
  • Kenneth K.W. To · W.W. Leung · Simon S.M. Ng
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    ABSTRACT: Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. While surgery remains the mainstay of treatment for early stage CRC, adjuvant chemotherapy is usually given to reduce the risk of recurrence after colectomy. Overexpression of a multidrug resistance (MDR) transporter ABCG2 in vitro has been shown to cause resistance to 5-fluorouracil (5-FU) and irinotecan, components of the most commonly adopted regimens for treating CRC. Both anticancer drugs are known ABCG2 substrates. An effective way to predict drug response may provide guidance for better cancer treatment. We investigated the effect of ABCG2 dysregulation on cancer cell sensitivity to chemotherapy using pairs of snap-frozen paraffin-embedded archival blocks of human colorectal cancer tissues and their matched non-cancerous colon tissues from CRC patients. In CRC patients responding to chemotherapy, the tumors were found to have remarkable lower ABCG2 expression than the adjacent normal colon tissues. On the contrary, the tumors from patients not responding to 5-FU-based chemotherapy have higher ABCG2 level than the adjacent normal tissues. The high ABCG2 expression in the tumor is associated with the concomitant overexpression of the mRNA binding protein HuR but a low expression of miR-519c because miR-519c is known to target both ABCG2 and HuR. Further investigation in CRC cell lines revealed that the ABCG2 overexpression was caused by an interplay between miR-519c, HuR and the length of the 3'untranslated region (UTR) of ABCG2. These parameters may be further developed as useful biomarkers to predict patient response to adjuvant chemotherapy. Besides being predictive biomarkers, the microRNAs and mRNA binding protein identified may also be potential drug targets for modulating ABCG2 to combat resistance in CRC chemotherapy.
    No preview · Article · Sep 2015 · Experimental Cell Research
  • Xu-Qin Li · Lin Wang · Yan Lei · Tao Hu · Fei-Long Zhang · Chi-Hin Cho · Kenneth K.W. To
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    ABSTRACT: With an aim to generate non-toxic, specific and highly potent multidrug resistance (MDR) modulators, a novel series of anthranilic acid amide-substituted tariquidar derivatives were synthesized. The new compounds were evaluated for their cytotoxicity toward normal human colon fibroblasts (CCD18-Co), human gastric epithelial cell line (HFE) and primary rat liver cells, and for their ability to inhibit P-gp/BCRP-mediated drug efflux and reversal of P-gp and BCRP-mediated MDR in parental and drug-resistant cancer cell lines (LCC6 MDR1, MCF-7 FLV1000, R-HepG2, SW620-Ad300). While tariquidar is highly toxic to normal cells, the new derivatives exhibited much lower or negligible cytotoxicity. Some of the new tariquidar derivatives inhibited both P-gp and BCRP-mediated drug efflux whereas a few of them bearing a sulfonamide functional group (1, 5, and 16) are specific to P-gp. The new compounds were also found to potentiate the anticancer activity of the transporter substrate anticancer drugs in the corresponding transporter-overexpressing cell lines. The extent of resistance reversal was found to be consistent with the transporter inhibitory effect of the new derivatives. To further understand the mechanism of P-gp and BCRP inhibition, the tariquidar derivatives were found to interact with the transporters using an antibody-based UIC2 or 5D3 shift assay. Moreover, the transporters-inhibiting derivatives were found to modulate the ATPase activities of the two MDR transporters. Our data thus advocate further development of the new compounds for the circumvention of MDR.
    No preview · Article · Aug 2015 · European Journal of Medicinal Chemistry
  • Kenneth K.W. To · Daniel C Poon · Yuming Wei · Fang Wang · Ge Lin · Li-Wu Fu
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    ABSTRACT: Cancer microenvironment is characterized by significantly lower oxygen concentration. This hypoxic condition is known to reduce drug responsiveness to cancer chemotherapy via multiple mechanisms, among which the upregulation of the ATP-binding cassette (ABC) efflux transporters confers resistance to a wide variety of structurally unrelated anticancer drugs. Vatalanib (PTK787/ZK22584) is a multitargeted tyrosine kinase inhibitor for all isoforms of VEGFR, PDGFR and c-Kit, which exhibit potent anticancer activity in vitro and in vivo. We investigated the potentiation effect of vatalanib on the anticancer activity of conventional cytotoxic drugs in colon cancer cell lines under both normoxic and hypoxic conditions. Mechanistically, vatalanib was found to inhibit ABCG2 and ABCB1 efflux activity, presumably by acting as a competitive inhibitor and interfering with their ATPase activity. Under hypoxic growth condition, ABCG2 and ABCB1-overexpressing cells sorted out by FACS technique as side population (SP) were found to be significantly more responsive to SN-38 (ABCG2 and ABCB1 substrate anticancer drug) in the presence of vatalanib. The anchorage independent soft agar colony formation capacity of the SP cells was remarkably reduced upon treatment with a combination of SN-38 and vatalanib, compared to SN-38 alone. However, vatalanib, at concentrations that produced the circumvention of the transporters-mediated resistance, did not appreciably alter ABCG2/ABCB1 mRNA or protein expression levels or the phosphorylation of Akt and extracellular signal-regulated kinase (ERK1/2). Our study thus advocates the further investigation of vatalanib for use in combination chemotherapy to eradicate drug-resistant cancer cells under hypoxia.
    No preview · Article · Aug 2015 · Biochemical pharmacology
  • Kenneth K. To · Daniel C. Poon · Yuming Wei · Fang Wang · Ge Lin · Li-wu Fu

    No preview · Article · Aug 2015 · Cancer Research
  • Kenneth K.W. To · Wing Wah Leung · Simon S.M. Ng

    No preview · Article · Aug 2015 · Cancer Research
  • Kenneth K W To · Daniel C Poon · Yuming Wei · Fang Wang · Ge Lin · Liwu Fu
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    ABSTRACT: Background and purpose: Pelitinib is a potent irreversible EGFR TK inhibitor currently in clinical trials for the treatment of lung cancer. Hyperthermia has been applied concomitantly with chemotherapy and radiotherapy to enhance treatment outcome. In this study, we investigated the ability of the combination of pelitinib with other conventional anticancer drugs to specifically target cancer cells with up-regulated efflux transporters ABCB1/ABCG2 after hyperthermia as a novel way to eradicate the cancer stem-like cells responsible for cancer recurrence. Experimental approach: Alterations in intracellular topotecan accumulation, the efflux of fluorescent probe substrates, expression and ATPase activity of ABCB1/ABCG2 and tumoursphere formation capacity of side population (SP) cells sorted after hyperthermia were examined to elucidate the mechanism of pelitinib-induced chemosensitization. Key results: While pelitinib did not modulate ABCB1/ABCG2 expressions, the combination of pelitinib with transporter substrate anticancer drugs induced more marked apoptosis, specifically in cells exposed to hyperthermia. The flow cytometric assay showed that both ABCB1- and ABCG2-mediated drug effluxes were significantly inhibited by pelitinib in a concentration-dependent manner. The inhibition kinetics suggested that pelitinib is a competitive inhibitor of ABCB1/ABCG2, which is consistent with its ability to stimulate their ATPase activity. SP cells sorted after hyperthermia were found to be more resistant to anticancer drugs, presumably due to the up-regulation of ABCB1 and ABCG2. Importantly, pelitinib specifically enhanced the chemosensitivity but reduced the tumoursphere formation capacity of these SP cells. Conclusions and implications: This study demonstrated a novel approach, exploiting drug resistance, to selectively kill cancer stem-like cells after hyperthermia.
    No preview · Article · Jul 2015 · British Journal of Pharmacology
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    ABSTRACT: The capability of monitoring the differentiation process in living stem cells is crucial to the understanding of stem cell biology and the practical application of stem-cell-based therapies, yet conventional methods for the analysis of biomarkers related to differentiation require a large number of cells as well as cell lysis. Such requirements lead to the unavoidable loss of cell sources and preclude real-time monitoring of cellular events. In this work, we report the detection of microRNAs (miRNAs) in living human mesenchymal stem cells (hMSCs) by using polydopamine-coated gold nanoparticles (Au@PDA NPs). The PDA shell facilitates the immobilization of fluorescently labeled hairpin DNA strands (hpDNAs) that can recognize specific miRNA targets. The gold core and PDA shell quench the fluorescence of the immobilized hpDNAs, and subsequent binding of the hpDNAs to the target miRNAs leads to their dissociation from Au@PDA NPs and the recovery of fluorescence signals. Remarkably, these Au@PDA–hpDNA nanoprobes can naturally enter stem cells, which are known for their poor transfection efficiency, without the aid of transfection agents. Upon cellular uptake of these nanoprobes, we observe intense and time-dependent fluorescence responses from two important osteogenic marker miRNAs, namely, miR-29b and miR-31, only in hMSCs undergoing osteogenic differentiation and living primary osteoblasts but not in undifferentiated hMSCs and 3T3 fibroblasts. Strikingly, our nanoprobes can afford long-term tracking of miRNAs (5 days) in the differentiating hMSCs without the need of continuously replenishing cell culture medium with fresh nanoprobes. Our results demonstrate the capability of our Au@PDA–hpDNA nanoprobes for monitoring the differentiation status of hMSCs (i.e., differentiating versus undifferentiated) via the detection of specific miRNAs in living stem cells. Our nanoprobes show great promise in the investigation of the long-term dynamics of stem cell differentiation, identification and isolation of specific cell types, and high-throughput drug screening.
    Full-text · Article · Jun 2015 · Journal of the American Chemical Society
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    ABSTRACT: Multidrug resistance (MDR) develops in nearly all patients with colon cancer. The reversal of MDR plays an important role in the success of colon cancer chemotherapy. One of the commonest mechanisms conferring MDR is the suppression of apoptosis in cancer cells. This study investigated the sensitivity of cryptotanshinone (CTS) and dihydrotanshinone (DTS), two lipophilic tanshinones from a traditional Chinese medicine Salvia miltiorrhiza, in apoptosis-resistant colon cancer cells. Cell viability was measured by MTT assay. Cell cycle distribution and apoptosis were determined by flow cytometry. Protein levels were analyzed by western blot analysis. The formation of acidic vesicular organelles was visualized by acridine orange staining. Experimental results showed that multidrug-resistant colon cancer cells SW620 Ad300 were sensitive to both CTS and DTS in terms of cell death, but with less induction of apoptosis when compared with the parental cells SW620, suggesting that other types of cell death such as autophagy could occur. Indeed, the two tanshinones induced more LC3B-II accumulation in SW620 Ad300 cells with increased autophagic flux. More importantly, cell viability was increased after autophagy inhibition, indicating that autophagy induced by the two tanshinones was pro-cell death. Besides, the cytotoxic actions of the two tanshinones were p53-independent, which could be useful in inhibiting the growth of apoptosis-resistant cancer cells with p53 defects. The current findings strongly indicate that both CTS and DTS could inhibit the growth of apoptosis-resistant colon cancer cells through induction of autophagic cell death and p53-independent cytotoxicity. They are promising candidates to be further developed as therapeutic agents in the adjuvant therapy for colon cancer, especially for the apoptosis-resistant cancer types. Copyright © 2015 Elsevier GmbH. All rights reserved.
    No preview · Article · May 2015 · Phytomedicine: international journal of phytotherapy and phytopharmacology
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    ABSTRACT: Multidrug resistance (MDR) to chemotherapeutic drugs is a formidable barrier to the success of cancer chemotherapy. Expressions of ATP-binding cassette (ABC) transporters contribute to clinical MDR phenotype. In this study, we found that afatinib, a small molecule tyrosine kinase inhibitor (TKI) targeting EGFR, HER-2 and HER-4, reversed the chemoresistance mediated by ABCG2 in vitro, but had no effect on that mediated by multidrug resistance protein ABCB1 and ABCC1. In addition, afatinib, in combination with topotecan, significantly inhibited the growth of ABCG2- overexpressing cell xenograft tumors in vivo. Mechanistic investigations exhibited that afatinib significantly inhibited ATPase activity of ABCG2 and downregulated expression level of ABCG2, which resulted in the suppression of efflux activity of ABCG2 in parallel to the increase of intracellular accumulation of ABCG2 substrate anticancer agents. Taken together, our findings may provide a new and useful combinational therapeutic strategy of afatinib with chemotherapeutical drug for the patients with ABCG2 overexpressing cancer cells.
    Preview · Article · Nov 2014 · Oncotarget
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    ABSTRACT: Multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer drugs is an obstacle to successful chemotherapy. Overexpression of P-glycoprotein (P-gp), an ATP-binding cassette (ABC) membrane transporter, can mediate the efflux of cytotoxic drugs out of cancer cells, leading to MDR and chemotherapy failure. Thus, development of safe and effective P-gp inhibitors plays an important role in circumvention of MDR. This study investigated the reversal of P-gp mediated multidrug resistance in colon cancer cells by five tanshinones including tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone and miltirone isolated from Salvia miltiorrhiza (Danshen), known to be safe in traditional Chinese medicine.
    No preview · Article · Sep 2014 · Phytomedicine: international journal of phytotherapy and phytopharmacology
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    ABSTRACT: The overexpression of ATP-binding cassette (ABC) transporters often leads to the development of multidrug resistance (MDR), which is the major factor contributing to the failure of chemotherapy. The objective of this study was to investigate the enhancement of CEP-33779, a small-molecule inhibitor of Janus kinase 2 (JAK2), on the efficacy of conventional chemotherapeutic agents in MDR cells with overexpression of P-glycoprotein (ABCB1), multidrug resistance-associated protein 1 (ABCC1) and breast cancer resistance protein (ABCG2). Our results showed that CEP-33779, at nontoxic concentrations, significantly sensitized ABCB1 overexpressing MDR cells to its anticancer substrates. CEP-33779 significantly increased intracellular accumulation and decreased the efflux of doxorubicin by inhibiting the ABCB1 transport function. Furthermore, CEP-33779 did not alter the expression of ABCB1 both at protein and mRNA levels but did stimulate the activity of ABCB1 ATPase. CEP-33779 was predicted to bind within the large hydrophobic cavity of homology modeled ABCB1. In addition, the down-regulation of JAK2 by shRNA altered neither the expression of ABCB1 nor the cytotoxic effect of chemotherapeutic agents in ABCB1-overexpressing cells. Significantly, CEP-33779 enhanced the efficacy of vincristine against the ABCB1-overexpressing and drug resistant KBv200 cell xenograft in nude mice. In conclusion, we conclude that CEP-33779 enhances the efficacy of substrate drugs in ABCB1-overexpressing cells by directly inhibiting ABCB1 transport function. The findings encouraged to further study on the combination therapy of CEP-33779 with conventional chemotherapeutic agents in ABCB1 mediated-MDR cancer patients.
    No preview · Article · Jul 2014 · Biochemical pharmacology
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    ABSTRACT: Cancer stem-like cells (CSC) have garnered significant attention as a therapeutic focus, based on evidence they may represent an etiologic root of treatment-resistant cells. Indeed, expression of the multidrug resistance protein ABCG2 confers chemoresistance to CSC where it serves as a potential biomarker and therapeutic target. Here we show that afatinib, a small molecule inhibitor of the tyrosine kinases EGFR, HER-2 and HER-4, preferentially eliminated side population (SP) cells with CSC character, in both cell lines or patient-derived leukemia cells, by decreasing ABCG2 expression. In these cells afatinib also acted in parallel to suppress self-renewal capacity and tumorigenicity. Combining afatinib with the DNA damaging drug topotecan enhanced the antitumor effect of topotecan in vitro and in vivo. Mechanistic investigations suggested that ABCG2 suppression by afatinib did not proceed by proteolysis through the ubiquitin-dependent proteosome, lysosome or calpain. Instead, we found that afatinib increased DNA methyltransferase activity, thereby leading to methylation of the ABCG2 promoter and to a decrease in ABCG2 message level. Taken together, our results advocate the use of afatinib in combination with conventional chemotherapeutic drugs to improve efficacy by improving CSC eradication.
    Full-text · Article · Jun 2014 · Cancer Research
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    ABSTRACT: Multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters through efflux of antineoplastic agents from cancer cells is a major obstacle to successful cancer chemotherapy. The inhibition of these ABC transporters is thus a logical approach to circumvent MDR. There has been intensive research effort to design and develop novel inhibitors for the ABC transporters to achieve this goal. In the present study, we evaluated the ability of UMMS-4 to modulate P-glycoprotein (P-gp/ABCB1)-, breast cancer resistance protein (BCRP/ABCG2)- and multidrug resistance protein (MRP1/ABCC1)-mediated MDR in cancer cells. Our findings showed that UMMS-4, at non-cytotoxic concentrations, apparently circumvents resistance to ABCB1 substrate anticancer drugs in ABCB1-overexpressing cells. When used at a concentration of 20 μmol/L, UMMS-4 produced a 17.53-fold reversal of MDR, but showed no effect on the sensitivity of drug-sensitive parental cells. UMMS-4, however, did not significantly alter the sensitivity of non-ABCB1 substrates in all cells and was unable to reverse ABCG2- and ABCC1-mediated MDR. Additionally, UMMS-4 profoundly inhibited the transport of rhodamine 123 (Rho 123) and doxorubicin (Dox) by the ABCB1 transporter. Furthermore, UMMS-4 did not alter the expression of ABCB1 at the mRNA and protein levels. In addition, the results of ATPase assays showed that UMMS-4 stimulated the ATPase activity of ABCB1. Taken together, we conclude that UMMS-4 antagonizes ABCB1-mediated MDR in cancer cells through direct inhibition of the drug efflux function of ABCB1. These findings may be useful for the development of safer and more effective MDR modulator.
    No preview · Article · Mar 2014 · American Journal of Cancer Research
  • Kenneth K W To · Brian Tomlinson
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    ABSTRACT: Multidrug resistance (MDR), usually mediated by overexpression of efflux transporters such as P-gp, ABCG2 and/or MRP1, remains a major obstacle hindering successful cancer chemotherapy. There has been great interest in the development of inhibitors towards these transporters to circumvent resistance. However, since the inhibition of transporter is not specific to cancer cells, a decrease in the cytotoxic drug dosing may be needed to prevent excess toxicity, thus undermining the potential benefit brought about by a drug efflux inhibitor. The design of potent MDR modulators specific towards resistant cancer cells and devoid of drug-drug interactions will be needed to effect MDR reversal. Recent evidence suggests that the PTEN/PI3K/Akt pathway may be exploited to alter ABCG2 subcellular localization, thereby circumventing MDR. Three PPARγ agonists (telmisartan, pioglitazone and rosiglitazone) that have been used in the clinics were tested for their effect on the PTEN/PI3K/Akt pathway and possible reversal of ABCG2-mediated drug resistance. The PPARγ agonists were found to be weak ABCG2 inhibitors by drug efflux assay. They were also shown to elevate the reduced PTEN expression in a resistant and ABCG2-overexpressing cell model, which inhibit the PI3K-Akt pathway and lead to the relocalization of ABCG2 from the plasma membrane to the cytoplasma, thus apparently circumventing the ABCG2-mediated MDR. Since this PPARγ/PTEN/PI3K/Akt pathway regulating ABCG2 is only functional in drug-resistant cancer cells with PTEN loss, the PPARγ agonists identified may represent promising agents targeting resistant cells for MDR reversal.
    No preview · Article · Aug 2013 · British Journal of Pharmacology
  • Kenneth K.W. To · Daniel C. Poon · XG Chen · Ge Lin · Li-wu Fu

    No preview · Article · Apr 2013 · Cancer Research
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    Kenneth K.W To · Daniel C Poon · X.G Chen · L.W Fu

    Preview · Article · Jan 2013

Publication Stats

1k Citations
287.81 Total Impact Points

Institutions

  • 1998-2016
    • The Chinese University of Hong Kong
      • Department of Pharmacy
      Hong Kong, Hong Kong
  • 2008-2012
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 2006-2008
    • National Cancer Institute (USA)
      • Center for Cancer Research
      Bethesda, MD, United States
  • 2004-2006
    • National Institutes of Health
      • • Center for Cancer Research
      • • Laboratory of Human Carcinogenesis
      Maryland, United States