Reversal of anticancer multidrug resistance by the ardeemins

Chou, Ting‐Chao; Depew, Kristopher M.; Zheng, Yu-Huang; Safer, Michelle L.; Chan, Daniel C.; Helfrich, Barbara A.; Zatorska, Danuta; Zatorski, Andrzej; Bornmann, William G.; Danishefsky, Samuel J.

doi:10.1073/pnas.95.14.8369

Cited by 67 publications

(36 citation statements)

References 19 publications

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“…This band completely disappeared on simultaneous incubation with either cyclosporine, BM-208 and BM-223 but only partially with verapamil and vinblastine. The excess of substrate used here (300-to 600-fold) to compete with [ 3 H]azidopine UV-labelling is in accordance with the range of concentrations previously reported (200-to 1,000-fold) [7,20,32]. Photolabelling of P-glycoprotein was inhibited only by a large excess of glibenclamide (about 2,000-fold) and even then not completely.…”

Section: Discussionsupporting

confidence: 86%

P-glycoprotein inhibition by glibenclamide and related compounds

Golstein¹,

Boom²,

Geffel

et al. 1999

Pfl�gers Archiv European Journal of Physiology

129

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Glibenclamide is well known to interact with the sulphonylurea receptor (SUR) and has been shown more recently to inhibit the cystic fibrosis transmembrane conductance regulator protein (CFTR), both proteins that are members of the ABC [adenosine 5'-triphosphate (ATP)-binding cassette] transporters. The effect of glibenclamide and two synthetic sulphonylcyanoguanidine derivatives (dubbed BM-208 and BM-223) was examined on P-glycoprotein, the major ABC transporter responsible for multidrug resistance (MDR) in cancer cells. To this end, we employed different cell lines that do or do not express P-glycoprotein, as confirmed by Western blotting: first, a tumour cell line (VBL600) selected from a human T-cell line (CEM) derived from an acute leukaemia; second, an epithelial cell line derived from a rat colonic adenocarcinoma (CC531(mdr+)) and finally, a non tumour epithelial cell line derived from the proximal tubule of the opossum kidney (OK). Glibenclamide and the two related derivatives inhibited P-glycoprotein because firstly, they acutely increased [3H]colchicine accumulation in P-glycoprotein-expressing cell lines only; secondly BM-223 reversed the MDR phenomenon, quite similarly to verapamil, by enhancing the cytotoxicity of colchicine, taxol and vinblastine and thirdly, BM-208 and BM-223 blocked the photoaffinity-labelling of P-glycoprotein by [3H]azidopine. Furthermore, glibenclamide is itself a substrate for P-glycoprotein, since the cellular accumulation of [3H]glibenclamide was low and substantially increased by addition of P-glycoprotein substrates (e. g., vinblastine and cyclosporine) only in the P-glycoprotein-expressing cell lines. We conclude that glibenclamide and two sulphonylcyanoguanidine derivatives inhibit P-glycoprotein and that sulphonylurea drugs would appear to be general inhibitors of ABC transporters, suggesting an interaction with some conserved motif.

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Section: Discussionsupporting

confidence: 86%

P-glycoprotein inhibition by glibenclamide and related compounds

Golstein¹,

Boom²,

Geffel

et al. 1999

Pfl�gers Archiv European Journal of Physiology

129

View full text Add to dashboard Cite

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“…The profile of the proteasome inhibitor bortezomib resembles that of cytotoxic agents, illustrating that inhibiting a well-defined target does not result in a targeted therapy when the target performs a general physiological function. Of all cell lines, SHP-77 was the least sensitive to doxorubicin, cisplatin, docetaxel, etoposide, vincristine and bortezomib (Figure 2C), which coincides with its expression of multiple multi-drug-resistance mechanisms [24]. HCT-15 and DLD-1 are different in karyotype but originate from the same patient [25].…”

Section: Resultsmentioning

confidence: 91%

Comparison of the Cancer Gene Targeting and Biochemical Selectivities of All Targeted Kinase Inhibitors Approved for Clinical Use

et al. 2014

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The anti-proliferative activities of all twenty-five targeted kinase inhibitor drugs that are in clinical use were measured in two large assay panels: (1) a panel of proliferation assays of forty-four human cancer cell lines from diverse tumour tissue origins; and (2) a panel of more than 300 kinase enzyme activity assays. This study provides a head-on comparison of all kinase inhibitor drugs in use (status Nov. 2013), and for six of these drugs, the first kinome profiling data in the public domain. Correlation of drug activities with cancer gene mutations revealed novel drug sensitivity markers, suggesting that cancers dependent on mutant CTNNB1 will respond to trametinib and other MEK inhibitors, and cancers dependent on SMAD4 to small molecule EGFR inhibitor drugs. Comparison of cellular targeting efficacies reveals the most targeted inhibitors for EGFR, ABL1 and BRAF(V600E)-driven cell growth, and demonstrates that the best targeted agents combine high biochemical potency with good selectivity. For ABL1 inhibitors, we computationally deduce optimized kinase profiles for use in a next generation of drugs. Our study shows the power of combining biochemical and cellular profiling data in the evaluation of kinase inhibitor drug action.

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“…This is apparently the reason why many drug combination clinical trials, such as the combination of anticancer natural product drug(s) ϩ MDR-reversing agent(s), have failed or reached inconclusive results. These disappointing results point to the conclusion that the in vitro and animal drug combinations should not be overlooked (Chou, 1994Chou et al, , 1998aChou et al, , 2005aChang et al, 2006). The complexities of clinical drug combination trials can be due to a variety of reasons: 1) the patient population varies in terms of sex, age, race, stage of disease, and the history of past treatments; 2) it is not ethical to treat patients with a placebo or suboptimal therapy of doses as required for the drug combination study design; and 3) death should not be allowed in clinical studies as a toxicity endpoint as in animal studies.…”

Section: F Drug Combination In Vitro In Vivo and In Clinicsmentioning

confidence: 99%