Acid ceramidase, an emerging target for anti-cancer and anti-angiogenesis

Sung Min Cho, Ho Jeong Kwon

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Sphingolipid metabolism plays an important role in determining the fate of a cell. Among several sphingolipid metabolites, ceramide is a key player in intracellular signal transduction. Ceramide is usually converted to various metabolites such as sphingomyelin, sphingosine, ceramide-1-phosphate, and glucosylceramide. If ceramide is accumulated in the cell, it induces apoptosis. On the other hand, its metabolite sphingosine is converted to sphingosine-1-phosphate (S1P), which promotes angiogenesis via G protein coupled receptor signaling. Therefore, the equilibrium in ceramide and S1P levels in cells plays an important role in angiogenesis as well as cell death. Acid ceramidase (AC) is a promising target protein in the development of multi-targeted anticancer drugs as its inhibition can simultaneously inhibit angiogenesis via the Akt and ERK 1/2 pathway and limit cancer growth through ceramide-induced apoptosis. Although some inhibitors of AC have been reported, they have not been proven effective for human therapy. Recent advancement in the elucidation of AC structure will facilitate the development of better inhibitors for treating human diseases.

Original languageEnglish
Pages (from-to)232-243
Number of pages12
JournalArchives of pharmacal research
Volume42
Issue number3
DOIs
Publication statusPublished - 2019 Mar 1

Fingerprint

Acid Ceramidase
Ceramides
Metabolites
Sphingolipids
Sphingosine
Neoplasms
Apoptosis
Glucosylceramides
Sphingomyelins
G-Protein-Coupled Receptors
Signal transduction
Cell death
Signal Transduction
Cell Death
Metabolism
Growth
Pharmaceutical Preparations
sphingosine 1-phosphate
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

Cite this

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title = "Acid ceramidase, an emerging target for anti-cancer and anti-angiogenesis",
abstract = "Sphingolipid metabolism plays an important role in determining the fate of a cell. Among several sphingolipid metabolites, ceramide is a key player in intracellular signal transduction. Ceramide is usually converted to various metabolites such as sphingomyelin, sphingosine, ceramide-1-phosphate, and glucosylceramide. If ceramide is accumulated in the cell, it induces apoptosis. On the other hand, its metabolite sphingosine is converted to sphingosine-1-phosphate (S1P), which promotes angiogenesis via G protein coupled receptor signaling. Therefore, the equilibrium in ceramide and S1P levels in cells plays an important role in angiogenesis as well as cell death. Acid ceramidase (AC) is a promising target protein in the development of multi-targeted anticancer drugs as its inhibition can simultaneously inhibit angiogenesis via the Akt and ERK 1/2 pathway and limit cancer growth through ceramide-induced apoptosis. Although some inhibitors of AC have been reported, they have not been proven effective for human therapy. Recent advancement in the elucidation of AC structure will facilitate the development of better inhibitors for treating human diseases.",
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Acid ceramidase, an emerging target for anti-cancer and anti-angiogenesis. / Cho, Sung Min; Kwon, Ho Jeong.

In: Archives of pharmacal research, Vol. 42, No. 3, 01.03.2019, p. 232-243.

Research output: Contribution to journalReview article

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AU - Cho, Sung Min

AU - Kwon, Ho Jeong

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N2 - Sphingolipid metabolism plays an important role in determining the fate of a cell. Among several sphingolipid metabolites, ceramide is a key player in intracellular signal transduction. Ceramide is usually converted to various metabolites such as sphingomyelin, sphingosine, ceramide-1-phosphate, and glucosylceramide. If ceramide is accumulated in the cell, it induces apoptosis. On the other hand, its metabolite sphingosine is converted to sphingosine-1-phosphate (S1P), which promotes angiogenesis via G protein coupled receptor signaling. Therefore, the equilibrium in ceramide and S1P levels in cells plays an important role in angiogenesis as well as cell death. Acid ceramidase (AC) is a promising target protein in the development of multi-targeted anticancer drugs as its inhibition can simultaneously inhibit angiogenesis via the Akt and ERK 1/2 pathway and limit cancer growth through ceramide-induced apoptosis. Although some inhibitors of AC have been reported, they have not been proven effective for human therapy. Recent advancement in the elucidation of AC structure will facilitate the development of better inhibitors for treating human diseases.

AB - Sphingolipid metabolism plays an important role in determining the fate of a cell. Among several sphingolipid metabolites, ceramide is a key player in intracellular signal transduction. Ceramide is usually converted to various metabolites such as sphingomyelin, sphingosine, ceramide-1-phosphate, and glucosylceramide. If ceramide is accumulated in the cell, it induces apoptosis. On the other hand, its metabolite sphingosine is converted to sphingosine-1-phosphate (S1P), which promotes angiogenesis via G protein coupled receptor signaling. Therefore, the equilibrium in ceramide and S1P levels in cells plays an important role in angiogenesis as well as cell death. Acid ceramidase (AC) is a promising target protein in the development of multi-targeted anticancer drugs as its inhibition can simultaneously inhibit angiogenesis via the Akt and ERK 1/2 pathway and limit cancer growth through ceramide-induced apoptosis. Although some inhibitors of AC have been reported, they have not been proven effective for human therapy. Recent advancement in the elucidation of AC structure will facilitate the development of better inhibitors for treating human diseases.

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