Cytochrome P450 1B1 Gene Polymorphisms as Predictors of Anticancer Drug Activity: Studies with <i>In vitro</i> Models

Laroche-Clary, Audrey; Morvan, Valérie Le; Yamori, Takao; Robert, Jacques

doi:10.1158/1535-7163.mct-10-0673

Cited by 19 publications

(16 citation statements)

References 17 publications

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“…CYP1B1 belongs to cytochrome p450 family, which is a multi-gene family of enzymes implicated in the metabolism of a diverse range of xenobiotics and endogenous compounds (24). Several researchers have proposed interesting concepts, in explaining the mechanisms of CYP1B1 induced cytotoxic effect reduction of chemotherapeutic drug (20,21,23,25), as other have mainly focused on CYP1B1 polymorphism in cancer process (22,32,33). Of particular interest, Patel et al reported that CYP1B1 may be regulated by cytokines, as interleukin-6 was observed to mediate of CYP1B1 upregulation via DNA methylation in colorectal cancer (34).…”

Section: Discussionmentioning

confidence: 99%

“…CXCR4 promotes cisplatin resistance through upregulation of CYP1B1. Increasing evidence has shown that many cytotoxic drugs are metabolized by cytochrome p450 (CYP) enzymes (17)(18)(19)(20)(21)(22)(23)(24)(25), we therefore explored the correlation of CXCR4 with CYP-related molecules (CYP1A1, CYP1A2, CYP1B1, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, CYP3A4, CYP3A5, CYP3A7 and CYP3A43) by bioinformatics (Table II). Our results indicated a positive correlation between CXCR4 and CYP1B1 with r= 0.616 (P<0.0001) and r= 0.538 (P<0.0001) in GSE30219 and GSE41271 datasets, respectively ( Fig.…”

Section: Cxcr4 Knockdown Enhances Cisplatin-induced Apoptosis and Inhmentioning

confidence: 99%

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CXCR4 promotes cisplatin-resistance of non-small cell lung cancer in a CYP1B1-dependent manner

Xie

Xiong

et al. 2016

Oncology Reports

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Chemoresistance is the main cause of treatment failure and high mortality in advanced lung cancer. Cisplatin, an important chemotherapeutic agent for lung cancer, has been observed to show enormously reduced chemotherapeutic efficacy owing to the development of chemoresistance. CXCR4, a stromal-derived-factor-1 specific chemokine receptor, is highly expressed in non-small cell lung cancer (NSCLC) tissues and participates in cancer progression by regulating cell growth, apoptosis or invasion. In this study, we therefore investigated whether CXCR4 plays a role in the cisplatin associated resistance in NSCLC. We detected the expression of CXCR4 in tissue specimens from 64 NSCLC patients by immunohistochemistry. Cisplatin-resistant NSCLC cells A549/DDP and its parental A549 cells were employed in this study. RNA interference was performed to silence the CXCR4. The influence of CXCR4 on tumor cell chemoresistance, apoptosis and growth, as well as the relationship between CXCR4 and the expression of cytochrome p450 associated molecule CYP1B1 in NSCLC were evaluated. Finally, we found CXCR4 was significantly highly expressed in cisplatin-resistant NSCLC patients and the A549/DDP cell line. CXCR4 inhibition by siRNA reversed chemoresistance and decreased tumor cell proliferation. Bioinformatics analysis showed that the expression of CYP1B1 had a positive correlation with CXCR4, the CYP1B1 silencing significantly decreased CXCR4 expression levels and cisplatin resistance. Immunohistochemistry also verified that CYP1B1 was upregulated in NSCLC tissues of cisplatin-resistant patients. In conclusion, our results indicate that overexpression of CXCR4 in NSCLC promotes cisplatin resistance via CXCR4-mediated CYP1B1 upregulation. Thus, it can be used as a potential therapeutic target in NSCLC chemoresistance patients and be used as a clinical predictor of cisplatin response.

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Section: Discussionmentioning

confidence: 99%

Section: Cxcr4 Knockdown Enhances Cisplatin-induced Apoptosis and Inhmentioning

confidence: 99%

CXCR4 promotes cisplatin-resistance of non-small cell lung cancer in a CYP1B1-dependent manner

Xie

Xiong

et al. 2016

Oncology Reports

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“…6,7 CYP1B1 gene polymorphisms and dysregulated CYP1B1 expression have been associated with the risk of developing lung and other cancers, 8,9 primary congenital glaucoma, 10 and systemic hypertension. 11 Multiple lines of evidence from both human and mouse show a role for CYP1B1 in the development of PAH.…”

Section: Introductionmentioning

confidence: 99%

Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension

Dempsie

MacRitchie

White

et al. 2013

Cardiovascular Research

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AimsPulmonary arterial hypertension (PAH) occurs more frequently in women than men. Oestrogen and the oestrogen-metabolising enzyme cytochrome P450 1B1 (CYP1B1) play a role in the development of PAH. Anorectic drugs such as dexfenfluramine (Dfen) have been associated with the development of PAH. Dfen mediates PAH via a serotonergic mechanism and we have shown serotonin to up-regulate expression of CYP1B1 in human pulmonary artery smooth muscle cells (PASMCs). Thus here we assess the role of CYP1B1 in the development of Dfen-induced PAH.Methods and resultsDfen (5 mg kg−1 day−1 PO for 28 days) increased right ventricular pressure and pulmonary vascular remodelling in female mice only. Mice dosed with Dfen showed increased whole lung expression of CYP1B1 and Dfen-induced PAH was ablated in CYP1B1−/− mice. In line with this, Dfen up-regulated expression of CYP1B1 in PASMCs from PAH patients (PAH-PASMCs) and Dfen-mediated proliferation of PAH-PASMCs was ablated by pharmacological inhibition of CYP1B1. Dfen increased expression of tryptophan hydroxylase 1 (Tph1; the rate-limiting enzyme in the synthesis of serotonin) in PAH-PASMCs and both Dfen-induced proliferation and Dfen-induced up-regulation of CYP1B1 were ablated by inhibition of Tph1. 17β-Oestradiol increased expression of both Tph1 and CYP1B1 in PAH-PASMCs, and Dfen and 17β-oestradiol had synergistic effects on proliferation of PAH-PASMCs. Finally, ovariectomy protected against Dfen-induced PAH in female mice.ConclusionCYP1B1 is critical in the development of Dfen-induced PAH in mice in vivo and proliferation of PAH-PASMCs in vitro. CYP1B1 may provide a novel therapeutic target for PAH.

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“…Various studies conducted on the CYP1B1 enzyme have indicated that the polymorphisms of this gene can change the enzymatic activity and the catalytic features of the enzymes (27,28). Considering four polymorphisms in the codon of Arg48Gly (CYP1B1*1), Ala119Ser (CYP1B1*2), Leu432Val (CYP1B1*3) and Asn453Ser (CYP1B1*4), it becomes clear that they have more hydroxylation activity than normal types, and all of them are related to the susceptibility of developing a cancer (27,(29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Polymorphisms on the Ala 119 Ser Gene Cytochrome P450 1B1*2 on the Susceptibility of Iranian Women to Develop Breast Cancer

2017

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Background: Cytochrome P450 IBI (CYP1B1) is involved in the metabolism of a wide range of internal and external substrates and also plays a key role in the metabolism of oestrogen. This enzyme is a factor that could potentially affect the likelihood of a person developing breast cancer. The aim of this study was to evaluate the correlation between polymorphism (RS1056827) and the occurrence of breast cancer in Iranian women. Methods:We used a case-control study design. After an initial evaluation, 79 women with breast cancer (the patient group) and 79 women without breast cancer (the control group) were selected to participate in the study. Their blood samples were then obtained, and a sample of their DNA was extracted. PCR-RELP was used to determine the genotypes of the participants. The data were subjected to statistical tests using the SPSS software package. Results:The results demonstrated that the frequency of the G allele in the patient and the control group were 34% and 69%, respectively. In addition, the frequency of the T allele in the patient and control group were 66% and 31%, respectively. The genotype frequency of TT, GG and TG in patients with breast cancer were 26.59%, 20.25% and 53.16%, respectively, and 22.79%, 60.76% and 16.45%, respectively, in the control group. There was a statistically meaningful correlation between the results of the genotypes in the patient and control groups. Conclusions:The results demonstrated that patients with the TT genotype are 3.85 times more likely to develop breast cancer. Therefore, the presence of this polymorphism could be one of the factors that lead to the development of breast cancer.

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Cytochrome P450 1B1 Gene Polymorphisms as Predictors of Anticancer Drug Activity: Studies with In vitro Models

Cited by 19 publications

References 17 publications

CXCR4 promotes cisplatin-resistance of non-small cell lung cancer in a CYP1B1-dependent manner

CXCR4 promotes cisplatin-resistance of non-small cell lung cancer in a CYP1B1-dependent manner

Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension

The Effect of Polymorphisms on the Ala 119 Ser Gene Cytochrome P450 1B1*2 on the Susceptibility of Iranian Women to Develop Breast Cancer

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