Abstract |
Oridonin (1), an active component isolated from the plant Rabdosia rubescens, has been reported to exhibit antitumor effects. In this study, the mechanism involved in 1-induced growth inhibition, including apoptosis and G(2)/M phase arrest, in human laryngeal carcinoma HEp-2 cells deficient in functional p53, was investigated for the first time. Compound 1 triggered the mitochondrial apoptotic pathway, as indicated by increased Bax/Bcl-2 ratios, reduction of mitochondrial membrane potential (DeltaPsi(m)), and substantial increase in apoptosis-inducing factor (AIF) and cytochrome c. Inhibition of caspase-9 in HEp-2 cells did not protect the cells from 1-induced apoptosis, and cleaved caspase-9 was not detected, indicating that apoptosis occurred via a caspase-9-independent pathway. The results also suggested that G(2)/M phase arrest and apoptosis mediated by 1 occurred via a p53-independent but in a p21/WAF1-dependent manner in HEp-2 cells. In addition, the generation of reactive oxygen species (ROS) was found to be a critical mediator in growth inhibition induced by 1. Taken together, the results indicate that oridonin (1) is a potentially effective agent for the treatment of laryngeal squamous cell carcinoma.
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Authors | Ning Kang, Jing-Hai Zhang, Feng Qiu, Sheng Chen, Shin-Ichi Tashiro, Satoshi Onodera, Takashi Ikejima |
Journal | Journal of natural products
(J Nat Prod)
Vol. 73
Issue 6
Pg. 1058-63
(Jun 25 2010)
ISSN: 1520-6025 [Electronic] United States |
PMID | 20496901
(Publication Type: Journal Article)
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Chemical References |
- Caspase Inhibitors
- Diterpenes, Kaurane
- Reactive Oxygen Species
- oridonin
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Topics |
- Apoptosis
(drug effects)
- Blotting, Western
- Carcinoma, Squamous Cell
- Caspase Inhibitors
- Cell Cycle
(drug effects)
- Diterpenes, Kaurane
(chemistry, pharmacology)
- Humans
- Isodon
(chemistry)
- Laryngeal Neoplasms
(drug therapy)
- Membrane Potential, Mitochondrial
(drug effects)
- Molecular Structure
- Reactive Oxygen Species
(analysis)
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