Simple non-ion-paired high-performance liquid chromatographic method for simultaneous quantitation of carboxylate and lactone forms of 14 new camptothecin derivatives

Sano, Kazumi; Yoshikawa, Megumi; Hayasaka, Shinya; Satake, Kurita; Ikegami, Yoji; Yoshida, Hisahiro; Ishikawa, Toshihisa; Sawada, Seigo; Tanabe, Shinzo

doi:10.1016/s1570-0232(03)00485-9

Cited by 26 publications

(29 citation statements)

References 19 publications

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“…22 Figure 3 demonstrates a strong correlation (r ϭ 0.95) between drug resistances ratios and inverse values of drug accumulation ratios. The drug accumulation ratio is defined as a relative value calculated from the drug accumulation level in PC-6/SN2-5H2 cells divided by that in PC-6 cells.…”

Section: Cellular Accumulation Of Cpt Analogues and Drug Resistance Pmentioning

confidence: 92%

“…After centrifugation, CPT analogues in the resulting supernatant were measured by the HPLC method. 22 The HPLC system consisted of a Jasco PU-1580 pump, a Jasco FP-920 fluorescence detector (Jasco, Tokyo, Japan) and a Shimadzu C-R4A integrator (Shimadzu, Kyoto, Japan). Isocratic elution was performed using a Mightysil RP-18 (L) GP column (5 m, 4.6 ϫ 150 mm ID; Kanto Chemical, Tokyo) with a guard column (5 m, 4.6 ϫ 5 mm ID).…”

Section: Measurement Of Intracellular Accumulation Of Sn-38 Analoguesmentioning

confidence: 99%

“…18 A suspension of plasma membrane vesicles (50 g of protein) was incubated with 2.5 M CPT analogues for 5 min at 37°C, after which the uptake of CPT analogues was determined by using HPLC. 22 Briefly, the transport buffer comprised CPT analogues, 250 mM sucrose, 10 mM MgCl 2 , 0.2 mM CaCl 2 , 10 mM HEPES/ Tris (pH 7.4), 10 mM creatine phosphate and 100 g/ml creatine kinase in the presence or absence of 5 mM ATP. After preincubation for 2 min at 37°C, the vesicle suspension (50 g protein) was incubated with the transport buffer.…”

Section: Vesicle Transportmentioning

confidence: 99%

“…The uptake of substrate into the membrane vesicles was determined by the HPLC method. 22 The uptake in the absence of ATP is deducted from that in the presence of ATP, and an amount greater than that in parental cells from the ABCG2-overexpressing cell line is referred to as ATP-dependent uptake. The correlation coefficient is determined by fitting the data to the linear regression line.…”

Section: Vesicle Transportmentioning

confidence: 99%

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Novel camptothecin analogues that circumvent ABCG2‐associated drug resistance in human tumor cells

Yoshikawa

Ikegami

Hayasaka

et al. 2004

Intl Journal of Cancer

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Key words: SN-38; CPT analogue; ABCG2; SAR; DNA topoisomerase I inhibitorCamptothecin (CPT) is an antitumor alkaloid that was originally isolated from Camptotheca acuminata, a tree native to southern China. 1 CPT has been demonstrated to inhibit mammalian DNA topoisomerase I (Topo I), the nuclear enzyme that changes the topologic state of duplex DNA by single-strand breakage and resealing. Stabilization of the covalent Topo I-DNA complex (so-called cleavable complex) by CPT is a critical step in its antitumor action where Topo I-mediated DNA breaks are induced via prevention of DNA relegation. 2 Clinical and preclinical studies, however, revealed reversible bone marrow depression and hemorrhagic cystitis as the major dose-limiting toxicities of CPT. Thus, efforts have been directed at finding new CPT analogues with higher antitumor activity and less toxicity.Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin; CPT-11) has been synthesized and developed as a new water-soluble analogue of CPT with wide-spectrum antitumor activity against many types of human tumor cells. 3,4 CPT-11 is a prodrug, the antitumor activity of which is exerted by 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of CPT-11. 5 Despite enormous expense and efforts spent on the development of cancer chemotherapies, acquired and intrinsic drug resistance in tumors is the major obstacle to long-term sustained patient response to chemotherapy. Hitherto several mechanisms for the resistance to SN-38 and its analogues have been proposed, e.g., mutations or decreased expression of Topo I, increased expression of the UGT1A protein or single nucleotide polymorphisms (SNPs) of the UGT1A gene, increased activity of O 6 -methylguanine-DNA-methyltransferase, a DNA repair protein, decreased activity of carboxylesterase that catalyzes the biosynthesis of SN-38 from CPT-11 in the plasma and liver and overexpression of drug export pumps. 6 -11 It has been documented that several ATP-binding cassette (ABC) transporters, such as P-glycoprotein (ABCB1/MDR1/P-gp) and multidrug resistance-associated protein 1 (ABCC1/MRP1), can cause drug resistance in tumor cells by actively extruding antitumor drugs. 12,13 Recently, a novel ABC transporter, ABCG2, also known as breast cancer-resistant protein (BCRP/MXR1/ ABCP), has been discovered in drug-resistant cell lines selected for by mitoxantrone or Topo I inhibitors. 14,15 Overexpression of ABCG2 has been shown to confer resistance to doxorubicin, mitoxantrone and various CPT analogues. 14,16,17 In a recent study with plasma membrane vesicles prepared from ABCG2-overexpressing SN-38-selected human small cell lung carcinoma cells, we found that ABCG2 transported SN-38 and its glucuronide metabolite in an ATP-dependent manner. 18 Thus, it is highly likely that ABCG2 actively extrudes SN-38 from tumor cells and thereby confers drug resistance.To circumvent ABCG2-associated drug resistance, in the present study we have synthesized a total of 14 different analogues of CPT and examine...

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Section: Cellular Accumulation Of Cpt Analogues and Drug Resistance Pmentioning

confidence: 92%

Section: Measurement Of Intracellular Accumulation Of Sn-38 Analoguesmentioning

confidence: 99%

Section: Vesicle Transportmentioning

confidence: 99%

Section: Vesicle Transportmentioning

confidence: 99%

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Novel camptothecin analogues that circumvent ABCG2‐associated drug resistance in human tumor cells

Yoshikawa

Ikegami

Hayasaka

et al. 2004

Intl Journal of Cancer

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“…HPLC analysis was performed according to Sano et al [27] to measure both the lactone and carboxylate forms of CPT-11 and SN-38. Briefly, CPT-11 was separated by using a LC-2000 plus series (JASCO, Tokyo, Japan) equipped with a Capcell Pak C18 column (4.6 × 250 mm, 5 µm; SHISEIDO, Tokyo, Japan) maintained at 30°C.…”

Section: Methodsmentioning

confidence: 99%

Gefitinib Enhances the Antitumor Activity of CPT-11 in vitro and in vivo by Inhibiting ABCG2 but Not ABCB1: A New Clue to Circumvent Gastrointestinal Toxicity Risk

Inoue¹,

Ikegami²,

Sano³

et al. 2013

Chemotherapy

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Background: Despite the potent antitumor activity of CPT-11, late-onset diarrhea owing to enterohepatic circulation of SN-38 is a critical issue. Methods: We aimed to evaluate the inhibitory potency of gefitinib against the ABCB1- or ABCG2-mediated excretion of CPT-11 and its active metabolite SN-38 in vitro and in vivo. Results: Gefitinib dose-dependently enhanced the antiproliferation activity of SN-38 in vitro by inhibiting ABCG2. The inhibitory effect of gefitinib on ABCB1 was marginal. When both CPT-11 and gefitinib were administered orally to nude mice bearing human lung cancer PC-6 cells, tumor growth was markedly suppressed. By gefitinib coadministration, the lactone forms of both CPT-11 and SN-38 in the tumor tissue increased more than 2-fold. Conclusions: Gefitinib significantly enhances the antitumor efficacy of CPT-11 and its tumor distribution in vivo. Coadministration of gefitinib may provide a new means to reduce the dose of CPT-11 and to circumvent the gastrointestinal toxicity risk.

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LC‐MS Bioanalysis of Interconvertible Compounds

Merbel

2013

Handbook of LC‐MS Bioanalysis

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Simple non-ion-paired high-performance liquid chromatographic method for simultaneous quantitation of carboxylate and lactone forms of 14 new camptothecin derivatives

Cited by 26 publications

References 19 publications

Novel camptothecin analogues that circumvent ABCG2‐associated drug resistance in human tumor cells

Novel camptothecin analogues that circumvent ABCG2‐associated drug resistance in human tumor cells

Gefitinib Enhances the Antitumor Activity of CPT-11 in vitro and in vivo by Inhibiting ABCG2 but Not ABCB1: A New Clue to Circumvent Gastrointestinal Toxicity Risk

LC‐MS Bioanalysis of Interconvertible Compounds

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