Abstract
Shikonin has been demonstrated to exhibit anti-cancer activity, but the underlying
mechanisms are poorly understood. In this report, we showed that the administration
of shikonin could result in the induction of apoptotic cell death of human hepatoma
cell line, SK-Hep-1. As evident by the flow-cytometric studies, shikonin has the capability
of generating increased amounts of intracellular reactive oxygen species (ROS) during
the early stage of this apoptotic process (ca. one-hour), and subsequently accompanied
by the dissipation of mitochondrial transmembrane potential (ΔΨm ) at 3 hours. Further studies indicated that this apoptotic process could effectively
be protected by the pretreatment of shikonin-treated cells with glutathione (GSH)
and N -acetylcysteine (NAC), a precursor of GSH, but not by cyclosporin A (CyA), an inhibitor
of mitochondrial permeability transition (MPT) pore. These data further proved that
ROS-mediated oxidative stress was the pivotal element involved in the induction of
apoptosis of SK-Hep-1 cells. Taken together, we suggest that shikonin-induced apoptosis
of SK-Hep-1 cells proceeds by an oxidative stress-mediated pathway.
Key words
Shikonin -
Lithospermum erythrorhizon
- Boraginaceae - Apoptosis - reactive oxygen species - mitochondrial transmembrane
potential
References
Lithospermum erythrorhizon induced apoptosis in HL60 human premyelocytic leukemia cell line.
Planta Medica.
1999;
65
532-5
tzliu@mail.cgu.edu.tw
