Effects of the ABCG2 and ABCB1 drug transporter polymorphisms on the pharmacokinetics of bicalutamide in humans

Kim, Kyoung Ah; Jung, Yu; Lee, Hae Mi; Joo, Hyun Jin; Park, Ji Young

doi:10.1016/j.cca.2014.08.006

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…Moreover, in c.34AA homozygotes, the plasma C max and AUC values of rosuvastatin were significantly higher than those with c.34GG homozygotes, indicating that the c.34G.A variant also plays a significant role in the rosuvastatin pharmacokinetics. Recently, Kim et al (2015) reported that the ABCG2 c.421C.A variant significantly influenced the pharmacokinetics of bicalutamide in a gene dose-dependent manner but that c.34G.A did not have such an effect on healthy Korean male subjects. It is unclear whether the lack of change in the bicalutamide pharmacokinetics in subjects with the c.34AA genotype was due to the small sample size of the study or a drug-specific action of the ABCG2 genetic variants.…”

Section: Discussionmentioning

confidence: 99%

Marked Alteration of Rosuvastatin Pharmacokinetics in Healthy Chinese with ABCG2 34G>A and 421C>A Homozygote or Compound Heterozygote

Wan

Guo

et al. 2015

J Pharmacol Exp Ther

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Rosuvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor used to lower blood low-density lipoprotein cholesterol, is a substrate of the membrane ABCG2 exporter. ABCG2 variants have been shown to alter rosuvastatin disposition. The objective of this study is to determine the impact of ABCG2 34/421 compound haplotypes on rosuvastatin pharmacokinetics in healthy Chinese volunteer subjects. Eight hundred healthy Chinese males were genotyped by polymerase chain reaction-pyrosequencing for ABCG2 34G.A, ABCG2 421C.A, SLCO1B1 521T.C, and CYP2C9*3 variants. Sixty-two male subjects with wild-type SLCO1B1 c.521TT and CYP2C9*3 were recruited for this pharmacokinetic study of rosuvastatin. A single oral dose of 10 mg rosuvastatin was administrated to each subject, and blood samples were collected before and at various time points after drug administration. Plasma concentration of rosuvastatin was determined by high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic analysis was carried out using the WinNonlin program. In Chinese males, high allele frequency of ABCG2 c.34G.A (0.275) and c.421C.A (0.282) was observed, resulting in a considerable portion (23.3%) of subjects being ABCG2 34/421 compound heterozygotes. Compared with subjects with ABCG2 wild-type (c.34GG/421CC), plasma rosuvastatin C max and area under the curve, AUC 0-' , were significantly higher, while the apparent oral clearance, CL/F, was significantly lower in subjects with c.34AA, c.421AA, and c.34GA/ 421CA genotypes. Both t 1/2 and T max were similar among subjects with different genotypes. A high frequency of ABCG2 c.34G.A and c.421C.A variants was present in Chinese males, and the disposition of rosuvastatin was significantly affected by both variants. These data suggest that it is advisable to genotype these variants when prescribing rosuvastatin to Chinese subjects, leading to a precise dose for each individual.

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Section: Discussionmentioning

confidence: 99%

Marked Alteration of Rosuvastatin Pharmacokinetics in Healthy Chinese with ABCG2 34G>A and 421C>A Homozygote or Compound Heterozygote

Wan

Guo

et al. 2015

J Pharmacol Exp Ther

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“…In terms of the chemoresistance of PCa, multiple mechanisms have been emphasized. Androgen receptor (AR) axis [4,5], ATP-binding cassette sub-family G member 2 (ABCG2) [6,7] have indicated to promote the drug-resistant activity in human PCa, via several pivotal signaling pathways. A possible critical role of autophagy in cancer onset and progression has recently been underscored by several studies.…”

Section: Introductionmentioning

confidence: 99%

Ambra1 induces autophagy and desensitizes human prostate cancer cells to cisplatin

et al. 2019

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Prostate cancer (PCa), the second most mortal cancer from developed countries, presents a high level of chemo-resistance. There is emerging evidence underscores the critical role of autophagy in the onset, progression and chemo-resistance of PCa. In the present study, we investigated the possible role of a novel autophagy regulator, Activating Molecule in Beclin1-Regulated Autophagy1 (Ambra1), a novel ATG gene in the sensitivity or PCa cells to cisplatin. We explored the regulation by the Ambra1 manipulation on the induction of apoptosis and autophagy in human PCa DU145 cells in the presence of cisplatin, via up- or down-regulating Ambra1 expression. In addition, we examined the colony forming of DU145 cells post cisplatin treatment and Ambra1 manipulation. Our results demonstrated that the Ambra1 upregulation reduced, whereas Ambra1 knockdown increased the cisplatin-induced apoptosis, caspase 3 cleavage and PARP (poly ADP-ribose polymerase) cleavage. Interestingly, we also found significant autophagy induction in the cisplatin-treated DU145 cells, with increased autophagic vesicles, upregulated autophagy-related markers. However, the cisplatin-induced autophagy was upregulated by the Ambra1 overexpression or was downregulated by the Ambra1 knockdown. In addition, the colony forming was also positively regulated by Ambra1 in DU145 cells post cisplatin treatment. In conclusion, Ambra1 negatively regulates the cisplatin-induced apoptosis and the cisplatin-mediated growth reduction in DU145 cells, in association with the Ambra1-mediated autophagy promotion. It implies that Ambra1-mediated autophagy might be an important mechanism underlining the sensitivity reduction of PCa cells.

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“…A variety of mechanisms have been identified including mutations in tubulin binding regions and changes to the expression and function of apoptosis and cell cycle checkpoint proteins (e.g., Bcl-2 and p53) (22–24). In addition, upregulation and activation of EGFR and genes encoding P-glycoprotein such as ABCG2 have shown to lead to chemoresistance in several tumor types (25–27). The current study provides a novel mechanism that contributes towards the multiple pathways through which PCa cells develop chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

Bone Microenvironment Changes in Latexin Expression Promote Chemoresistance

Zhang

Osisami

Dai

et al. 2017

Molecular Cancer Research

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Although docetaxel (DOX) is the standard of care for advanced prostate cancer (PCa), most patients develop resistance to DOX. Therefore, elucidating the mechanism that underlies resistance to DOX is critical to enhance therapeutic intervention. Mining cDNA microarray from the PC-3 PCa cell line and its DOX-resistant derivative (PC3-TxR) revealed decreased latexin (LXN) expression in the resistant cells. LXN expression was inversely correlated with taxane resistance in a panel of PCa cell lines. LXN knockdown conferred DOX resistance to PCa cells in vitro and in vivo; whereas LXN overexpression reduced DOX resistance in several PCa cell lines. A mouse model of PCa demonstrated that PCa cells developed resistance to DOX in the bone microenvironment, but not the soft tissue microenvironment. This was associated with decreased LXN expression in PCa cells in the bone microenvironment compared to the soft tissue microenvironment. It was identified that bone stromal cells decreased LXN expression through methylation and induced chemoresistance in PCa in vitro. These findings reveal that a subset of PCa develops DOX resistance through loss of LXN expression associated with methylation and that the bone microenvironment promotes this drug resistance phenotype.

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Effects of the ABCG2 and ABCB1 drug transporter polymorphisms on the pharmacokinetics of bicalutamide in humans

Cited by 7 publications

References 26 publications

Marked Alteration of Rosuvastatin Pharmacokinetics in Healthy Chinese with ABCG2 34G>A and 421C>A Homozygote or Compound Heterozygote

Marked Alteration of Rosuvastatin Pharmacokinetics in Healthy Chinese with ABCG2 34G>A and 421C>A Homozygote or Compound Heterozygote

Ambra1 induces autophagy and desensitizes human prostate cancer cells to cisplatin

Bone Microenvironment Changes in Latexin Expression Promote Chemoresistance

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