Involvement of caspases and apoptosis-inducing factor in bufotalin-induced apoptosis of hep 3B cells

Chun-Li Su, Ting Yu Lin, Chun Nan Lin, Shen Jeu Won

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Bufotalin is one of the bufadienolides isolated from Formosan Ch'an Su, which is made of the skin and parotid glands of toads. Ingestion of toad venom results in severe morbidity and high mortality. Although Ch'an Su is clinically toxic, it has been used as an important traditional Chinese medicine for heart failure and pains. In this study, bufotalin-induced apoptosis in human hepatocellular carcinoma Hep 3B cells was investigated. The results indicate that externalization of phosphatidylserine, accumulation of sub-G1 cells, fragmentation of DNA, and formation of apoptotic bodies were observed in bufotalin-treated Hep 3B cells. The signaling pathway might be via the activation of caspase-8, increase in mitochondrial tBid, disruption of mitochondrial membrane potential, and translocation of apoptosis-inducing factor (AIF). Active caspase-8 might activate caspase-9 and caspase-3 leading to the cleavage of nuclear PARP. Presence of AIF and cleaved PARP in the nuclei might lead to DNA fragmentation. Caspase-8 inhibitor (Z-IETD) or wide-ranging caspase inhibitor (Z-VAD) significantly suppressed the bufotalin-induced apoptosis, while the anti-Fas neutralization antibody had no effect. These data suggest that bufotalin-induced apoptosis in Hep 3B cells might involve caspases and AIF.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalJournal of Agricultural and Food Chemistry
Volume57
Issue number1
DOIs
Publication statusPublished - 2009 Jan 14

Fingerprint

Apoptosis Inducing Factor
caspases
Caspases
apoptosis
Caspase 8
Apoptosis
caspase-8
Caspase Inhibitors
DNA Fragmentation
DNA fragmentation
cells
toads
Amphibian Venoms
Bufanolides
bufadienolides
skin glands
Caspase 9
Mitochondrial Membrane Potential
Poisons
parotid gland

Keywords

  • Apoptosis
  • Apoptosis-inducing factor
  • Bufotalin
  • Caspases
  • Ch'an Su
  • Mitochondria

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Cite this

Involvement of caspases and apoptosis-inducing factor in bufotalin-induced apoptosis of hep 3B cells. / Su, Chun-Li; Lin, Ting Yu; Lin, Chun Nan; Won, Shen Jeu.

In: Journal of Agricultural and Food Chemistry, Vol. 57, No. 1, 14.01.2009, p. 55-61.

Research output: Contribution to journalArticle

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N2 - Bufotalin is one of the bufadienolides isolated from Formosan Ch'an Su, which is made of the skin and parotid glands of toads. Ingestion of toad venom results in severe morbidity and high mortality. Although Ch'an Su is clinically toxic, it has been used as an important traditional Chinese medicine for heart failure and pains. In this study, bufotalin-induced apoptosis in human hepatocellular carcinoma Hep 3B cells was investigated. The results indicate that externalization of phosphatidylserine, accumulation of sub-G1 cells, fragmentation of DNA, and formation of apoptotic bodies were observed in bufotalin-treated Hep 3B cells. The signaling pathway might be via the activation of caspase-8, increase in mitochondrial tBid, disruption of mitochondrial membrane potential, and translocation of apoptosis-inducing factor (AIF). Active caspase-8 might activate caspase-9 and caspase-3 leading to the cleavage of nuclear PARP. Presence of AIF and cleaved PARP in the nuclei might lead to DNA fragmentation. Caspase-8 inhibitor (Z-IETD) or wide-ranging caspase inhibitor (Z-VAD) significantly suppressed the bufotalin-induced apoptosis, while the anti-Fas neutralization antibody had no effect. These data suggest that bufotalin-induced apoptosis in Hep 3B cells might involve caspases and AIF.

AB - Bufotalin is one of the bufadienolides isolated from Formosan Ch'an Su, which is made of the skin and parotid glands of toads. Ingestion of toad venom results in severe morbidity and high mortality. Although Ch'an Su is clinically toxic, it has been used as an important traditional Chinese medicine for heart failure and pains. In this study, bufotalin-induced apoptosis in human hepatocellular carcinoma Hep 3B cells was investigated. The results indicate that externalization of phosphatidylserine, accumulation of sub-G1 cells, fragmentation of DNA, and formation of apoptotic bodies were observed in bufotalin-treated Hep 3B cells. The signaling pathway might be via the activation of caspase-8, increase in mitochondrial tBid, disruption of mitochondrial membrane potential, and translocation of apoptosis-inducing factor (AIF). Active caspase-8 might activate caspase-9 and caspase-3 leading to the cleavage of nuclear PARP. Presence of AIF and cleaved PARP in the nuclei might lead to DNA fragmentation. Caspase-8 inhibitor (Z-IETD) or wide-ranging caspase inhibitor (Z-VAD) significantly suppressed the bufotalin-induced apoptosis, while the anti-Fas neutralization antibody had no effect. These data suggest that bufotalin-induced apoptosis in Hep 3B cells might involve caspases and AIF.

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