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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제21권 제6호
- 발행연도
- 2017.11
- 수록면
- 599 - 607 (9page)
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초록· 키워드
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Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak.
JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far more efficient than that of BCH in Saos2 cells.
Likewise, JPH203 and BCH inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard. Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2 cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells.
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참고문헌 (29)
참고문헌 신청
Christensen HN / 1990 / Role of amino acid transport and countertransport in nutrition and metabolism / Physiol Rev 70:43~77
McGivan JD / 1994 / Regulatory and molecular aspects of mammalian amino acid transport / Biochem J 299:321~334
Kanai Y / 1998 / Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen(CD98) / J Biol Chem 273:23629~23632
Segawa H / 1999 / Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity / J Biol Chem 274:19745~19751
Babu E / 2003 / Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters / J Biol Chem 278:43838~43845
McGivan JD / 1994 / Regulatory and molecular aspects of mammalian amino acid transport / Biochem J 299:321~334
Kanai Y / 1998 / Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen(CD98) / J Biol Chem 273:23629~23632
Segawa H / 1999 / Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity / J Biol Chem 274:19745~19751
Babu E / 2003 / Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters / J Biol Chem 278:43838~43845
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