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Inhibition of Proliferation of Human Fibroblast by δ-Aminolevulinic Acid (ALA) Derivatives through the Induction of Mitochondria Membrane Depolarization

δ-Aminolevulinic acid (ALA) 유도체들의 미토콘드리아 탈분극 유도에 의한 인간 섬유아세포의 세포분열 억제

  • Jun, Yong-woo (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University) ;
  • Han, Du-Gyeong (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University) ;
  • Lee, Jin-A (Department of Biological Science and Biotechnology, College of Life Science and Nano Technology, Hannam University) ;
  • Jo, Su-Yeon (WEDEA Co.) ;
  • Jang, Deok-Jin (Department of Ecological Science, College of Ecology and Environment, Kyungpook National University)
  • 전용우 (경북대학교 생태환경대학 생태과학과) ;
  • 한두경 (경북대학교 생태환경대학 생태과학과) ;
  • 이진아 (한남대학교 생명나노과학대학 시스템생명공학과) ;
  • 조수연 ((주)위디어) ;
  • 장덕진 (경북대학교 생태환경대학 생태과학과)
  • Received : 2015.09.08
  • Accepted : 2015.12.11
  • Published : 2015.12.27

Abstract

${\delta}$-Aminolevulinic acid (ALA) is an endogenous metabolite formed in the mitochondria from succinyl-CoA and glycine, and plays a key role in the living body as an intermediate of the compound in the porphyrin biosynthesis pathway. ALA has been commonly used in photodynamic therapy for several years, because ALA is of interest as a biodegradable mediator, a growth regulator, and an effective agent used in dermatology. Here, we determined which ALA derivatives were the most effective for the inhibition of the cell proliferation and growth of human fibroblast. As a result, we found that the treatment of ALA derivatives including ALA, ALAP (ALA phosphate salt), MAL (Methyl 5-aminolevulinate hydrochloride salt), PBGL (phophobilinogen lactam) and PBGH (phophobilinogen-HCl) could attenuate cell proliferation of human fibroblast cells. Among them, PBGH was the most effective derivative. In addition, PBGH treatment could induce mitochondrial membrane depolarization, leading to cell death of human fibroblast. These results suggest that mitochondrial membrane depolarization induced by ALA and PBGH treatment might be responsible for inhibition of cell proliferation and death. Taken together, our results propose the possibility that PBGH can be used as one of the effective drugs in human skin disease, psoriasis.

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References

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