Solute Carrier Transporters as Targets for Drug Delivery and Pharmacological Intervention for Chemotherapy

Nakanishi, Takeo; Tamai, Ikumi

doi:10.1002/jps.22576

Cited by 116 publications

(110 citation statements)

References 180 publications

(208 reference statements)

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“…The organic anion transporter polypeptide (OATP/SLCO) family members generally mediate Na + -independent transport of amphipathic organic anion compounds, including bile salts, steroid conjugates, thyroid hormones, and oligopeptides [5,6]. The physiological roles of these transporters are not yet fully understood, but there is compelling evidence that certain members of the OATP family promote cell proliferation and survival of human malignant tissues.…”

Section: Introductionmentioning

confidence: 99%

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Arakawa

Nakanishi

Yanagihara

et al. 2012

Biochemical Pharmacology

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The biological mechanisms underlying castration resistance of prostate cancer are not fully understood. In the present study, we examined the role of organic anion transporting polypeptides (OATPs) as importers of dehydroepiandrosterone sulfate (DHEAS) into cells to support growth under androgen-depleted conditions. Cell growth and mRNA expression of OATP genes were studied in human prostate cancer LNCaP and 22Rv1 cells under androgen-depleted conditions. The stimulatory effect of DHEAS on cell growth was investigated in LNCaP cells in which OATP1A2 had been silenced. Growth of both cell lines was stimulated by DHEAS and the effect was attenuated by STX64, an inhibitor of steroid sulfatase which can covert DHEAS to DHEA. OATP1A2 mRNA expression was increased most prominently among various genes tested in LNCaP cells grown in androgen-depleted medium. Similar results were obtained with 22Rv1 cells. Furthermore, the characteristics of

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Section: Introductionmentioning

confidence: 99%

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Arakawa

Nakanishi

Yanagihara

et al. 2012

Biochemical Pharmacology

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“…The assumption that the majority of administered drugs interact with membrane transporters located at the boundary between the intra end extracellular environment, became accepted over the years and now is well established (DeGorter et al, 2012;Giacomini et al, 2010;Han, 2011;Huang et al, 2008;Nakanishi and Tamai, 2011). Noteworthy, the brush border epithelia of intestine and kidney tubules have a very large surface in contact with the external environments from which drugs are absorbed after oral administration or reabsorbed after glomerular filtration.…”

Section: Introductionmentioning

confidence: 99%

Amino Acid Transporters in Drug Discovery

Scalise¹,

Pochini²,

Galluccio³

et al. 2014

Current Research in Drug Discovery

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Administered drugs interact with membrane transporters of epithelia, Blood Brain Barrier and other districts influencing their delivery and efficacy. Drugs can also be used as inhibitors of transporters involved in human pathology. Drug-transporter interactions are responsible of off-target effects contributing to toxicity. High Throughput Screening technologies increased the potential applications in therapy or in predicting side effects. These strategies will be helpful in reducing animal experimentation. The identification of transporters important for drug absorption, delivery and side effect production and the best technologies for studying interactions are the main goals in this field. Amino acid transporters are not yet considered in human therapy in spite of their involvement in several pathologies. The function of the amino acid transporters EAAT1, ASCT2, GLYT2, GLYT1, B0AT1, LAT1 and LAT2 is so far well characterized. Some structural data on these transporters have also been obtained by bioinformatics.Interactions of these proteins with several drugs have been well defined at the molecular level. Large scale and, in some cases, high throughput screening of pharmacological compounds make these transporters of particular interest and potential application in human health.

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“…Besides, several transporter proteins for amino acids such as leucine and glutamine have been well documented to be upregulated in many types of cancer cells, [3,4] showing their critical role in nutrient signaling to mTOR and cell growth [5]. In addition to amino acid transporter, we have shown that enhanced activity of peptide transport in cancer cells [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…In addition to amino acid transporter, we have shown that enhanced activity of peptide transport in cancer cells [6,7]. Thus, differential upregulation of influx transporter could be utilized not only to efficiently deliver their substrate drug with anti-tumor activity [3,7] or diagnostic markers [4,8,9], but also to shut off nutrient essential for cell growth; therefore, they can be promising target for a new chemotherapy. In this short review, we introduce our recent progresses regarding pathophysiological role of enhanced organic anion transporting polypeptides, OATPs, in cell proliferation of hormone-dependent breast and prostate cancers, implying pharmacological intervention of OATPs may contribute to efficient eradication of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

A Putative Role of Organic Anion Transporting Polypeptides (OATPs) In Cell Survival of Hormone-Dependent Breast and Prostate Cancers

Nakanishi¹

2013

Journal of Cancer Research and Therapeutic Oncology

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Transporter proteins classified into the solute carrier (SLC) transporter superfamily are essential for import of nutrients for cell survival in organisms. In the last two decades, compelling evidence has accumulated that SLC transporters interact with clinically important anticancer agents and contribute to their pharmacokinetics, particularly the biopharmaceutical processes of absorption, elimination and distribution. Furthermore, many SLC transporters have been shown to be differentially upregulated in cancer cells, and this may represent an adaptive response to altered nutritional requirements. Thus, it is likely to utilize them as carrier for efficient drug delivery as well as pharmacological target to shut off the essential nutrients for cell growth of malignant tumors. This short review will introduce organic anion transporting polypeptides which recognize endo-and exogenous organic anionic compounds and recent findings about their upregulation in cancer cells. Besides, OATP-mediated sulfate conjugates of steroid hormone may contribute to cell survival and adapted growth under hormonedepleted conditions. Better understandings of pathophysiological role of OATPs likely provide key information to overcome hormone-refractory breast and prostate tumors.

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Solute Carrier Transporters as Targets for Drug Delivery and Pharmacological Intervention for Chemotherapy

Cited by 116 publications

References 180 publications

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Amino Acid Transporters in Drug Discovery

A Putative Role of Organic Anion Transporting Polypeptides (OATPs) In Cell Survival of Hormone-Dependent Breast and Prostate Cancers

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