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 language | English (US) |
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Pages (from-to) | 132-144 |
Number of pages | 13 |
Journal | Biochemical Pharmacology |
Volume | 72 |
Issue number | 2 |
DOIs | |
State | Published - Jul 14 2006 |
Externally published | Yes |
Keywords
- Andrographolide
- Apoptosis
- Bax
- Bcl-2 family
- Bid
- Mitochondria
ASJC Scopus subject areas
- Biochemistry
- Pharmacology