Abstract
Herbal medicine is one of the forms of traditional medical practice. Traditional Chinese medicine (TCM) and traditional Vietnamese medicine (TVM) are well-known for their long-standing tradition of herbal medicine.Secreted by many species of blister beetle, most notably by the 'Spanish fly' (Lytta vesicatoria), cantharidin inhibits protein phosphatases 1 and 2A (PP1, PP2A). Blister beetle has been used in Asian traditional medicine to treat Molluscum contagiosum virus (MCV) infections and associated warts, and is now also used for cancer treatment. A combination of both genomic and postgenomic techniques was used in our studies to identify candidate genes affecting sensitivity or resistance to cantharidin. Cantharidin was not found to be related to multidrug resistance phenotype, suggesting its potential usefulness for the treatment of refractory tumors. Oxidative stress response genes diminish the activity of cantharidin by inducing DNA strand breaks which may be subject to base excision repair and induce apoptosis in a p53- and Bcl2-dependent manner.Cantharidin is one of many natural products used in traditional Chinese medicine and traditional Vietnamese medicine for cancer treatment. Combined methods of pharmaceutical biology and molecular biology can help elucidate modes of action of these natural products.
Highlights
Herbal medicine represents a traditional form of medical practice in human history
The microarray analyses were used to find the genes responsible for the action of cantharidin. These studies showed that many apoptosis-related genes and genes involved in DNA damage and repair correlated with the inhibition concentration 50% (IC50) values for cantharidin in the NCI cell line panel
The ability of Bcl-2 to protect against cantharidininduced apoptosis seen in this study indicates that DNA damage-triggered mitochondrial pathway is involved
Summary
Herbal medicine represents a traditional form of medical practice in human history. Current ethnobotany and ethnopharmacology focus on the systematic exploration of medicinal herbs among folk medicines [1]. There is an urgent need to develop new drugs with improved resistance modulation for tumor therapy It is the current situation in cancer chemotherapy in Western medicine that prompted us to study TCM and TVM. The microarray analyses were used to find the genes responsible for the action of cantharidin These studies showed that many apoptosis-related genes and genes involved in DNA damage and repair correlated with the IC50 values for cantharidin in the NCI cell line panel. We reported that cantharidin induces apoptosis by a p53-dependent mechanism in leukemia cells [24] Cantharidin causes both DNA single- and double-strand breaks. These data suggest that cantharidin treatment causes oxidative stress which damages DNA and triggers p53-dependent apoptosis. It is important to test whether this is a cancer cell that has acquired mutations in DNA repair pathways but retains wild-type p53 and sensitivity to oxidative stress
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