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Environ Toxicol Pharmacol. 2015 Mar;39(2):982-9. doi: 10.1016/j.etap.2015.03.003. Epub 2015 Mar 10.

Esculetin induces death of human colon cancer cells via the reactive oxygen species-mediated mitochondrial apoptosis pathway.

Author information

1
School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea.
2
School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea. Electronic address: sukjucho@gmail.com.
3
School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea. Electronic address: jinwonh@jejunu.ac.kr.

Abstract

The present study investigated the apoptotic effects of esculetin, a coumarin derivative, on the human colon cancer cell line HT-29. Esculetin had cytotoxic effects on HT-29 cells in a dose- and time-dependent manner; treatment with 55 μg/mL esculetin reduced cell viability by 50%. Esculetin induced apoptosis, as evidenced by apoptotic body formation, an increased percentage of cells in sub-G1 phase, and DNA fragmentation. Moreover, esculetin increased mitochondrial membrane depolarization, released cytochrome c into cytosol, and modulated the expression of apoptosis-associated proteins, resulting in reduced expression of B cell lymphoma-2, increased expression of Bcl-2-associated X protein, and activation of caspase-9 and caspase-3. Esculetin induced the formation of reactive oxygen species; however, treatment with an antioxidant reduced the apoptotic cell death induced by esculetin treatment. In addition, esculetin activated mitogen-activated protein kinases and specific inhibitors of these kinases abrogated the reduction in cell viability induced by esculetin treatment.

KEYWORDS:

Apoptosis; Esculetin; Human colon cancer; Reactive oxygen species; Signal pathway

PMID:
25818986
DOI:
10.1016/j.etap.2015.03.003
[Indexed for MEDLINE]

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