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Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters
T Tengchaisri1, R Chawengkirttikul, N Rachaphaew
1Laboratory of Immunology, Chulabhorn Research Institute, Bangkok, Thailand.
Abstract:
One of the diverse biological activities of triptolide, a diterpene from Tripterygium wilfordii, is its antitumor effect. We recently reported its in vitro cytotoxicity against several cultured tumor cell lines. Limited availability of purified fraction has prevented detailed investigation on its antitumor activity. In the present study, we showed by in vitro cytotoxicity assay and in vivo inhibition of tumor growth in hamsters that the triptolide was also highly effective against cholangiocarcinoma, a highly fatal tumor predominantly occurring in developing countries. Its ED50 for these hamster cholangiocarcinoma cell lines was found to be as low as 0.05 microg/ml. The compound was highly potent in the induction of apoptotic death in these tumor cells. DNA fragmentation and disintegrating apoptotic cells could be observed within 24 h of exposure to 0.5 microg/ml triptolide. The compound was tested against the growth of cholangiocarcinoma in a hamster model. A significant growth inhibition (P < 0.05) was noted in triptolide-treated hamsters (each of the 10 animals received 10 injections for a total of 1.2 mg/animal). At the time of sacrifice 1 month after the initial injection, the mean tumor mass of the treated group was only 20-25% of that of the control group.
Insights
Triptolide, a compound from Tripterygium wilfordii, shows potent antitumor effects against cholangiocarcinoma. This study demonstrates its effectiveness in inhibiting tumor growth and inducing cancer cell death in preclinical models.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Triptolide, a diterpenoid from Tripterygium wilfordii, possesses known antitumor properties.
- Previous research indicated triptolide's in vitro cytotoxicity against various tumor cell lines.
- Limited availability of purified triptolide has hindered comprehensive antitumor activity investigations.
Purpose of the Study:
- To evaluate the efficacy of triptolide against cholangiocarcinoma, a highly fatal cancer.
- To investigate triptolide's mechanism of action, including induction of apoptosis in tumor cells.
- To assess triptolide's antitumor activity in a hamster model of cholangiocarcinoma.
Main Methods:
- In vitro cytotoxicity assays were performed on hamster cholangiocarcinoma cell lines.
- Apoptosis induction was assessed by observing DNA fragmentation and cell morphology.
- In vivo tumor growth inhibition was evaluated in a hamster cholangiocarcinoma model.
Main Results:
- Triptolide exhibited high cytotoxicity against cholangiocarcinoma cell lines with an ED50 of 0.05 microg/ml.
- Triptolide potently induced apoptotic cell death, evidenced by DNA fragmentation within 24 hours.
- Significant inhibition of cholangiocarcinoma tumor growth was observed in vivo (P < 0.05).
Conclusions:
- Triptolide demonstrates significant preclinical efficacy against cholangiocarcinoma.
- The compound effectively inhibits tumor growth and induces apoptosis in cancer cells.
- Triptolide represents a potential therapeutic agent for cholangiocarcinoma treatment.