Critical role of pro-apoptotic Bcl-2 family members in andrographolide-induced apoptosis in human cancer cells

Jing Zhou, Siyuan Zhang, Ong Choon-Nam, Han Ming Shen

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess potent anti-inflammatory activity. In this study, Andro induced apoptosis in human cancer cells via activation of caspase 8 in the extrinsic death receptor pathway and subsequently with the participation of mitochondria. Andro triggered a caspase 8-dependent Bid cleavage, followed by a series of sequential events including Bax conformational change and mitochondrial translocation, cytochrome c release from mitochondria, and activation of caspase 9 and 3. Inhibition of caspase 8 blocked Bid cleavage and Bax conformational change. Consistently, knockdown of Bid protein using small interfering RNA (siRNA) technique suppressed Andro-induced Bax conformational change and apoptosis. In conclusion, the pro-apoptotic Bcl-2 family members (Bid and Bax) are the key mediators in relaying the cell death signaling initiated by Andro from caspase 8 to mitochondria and then to downstream effector caspases, and eventually leading to apoptotic cell death.

Original languageEnglish (US)
Pages (from-to)132-144
Number of pages13
JournalBiochemical Pharmacology
Volume72
Issue number2
DOIs
StatePublished - Jul 14 2006
Externally publishedYes

Keywords

  • Andrographolide
  • Apoptosis
  • Bax
  • Bcl-2 family
  • Bid
  • Mitochondria

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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