Induction of G2/M Phase Arrest and Apoptosis by Oridonin in Human Laryngeal Carcinoma Cells

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 G2/M phase arrest, in human laryngeal carcinoma HEp-2 cells deficient in functio...

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Bibliographic Details
Published inJournal of natural products (Washington, D.C.) Vol. 73; no. 6; pp. 1058 - 1063
Main Authors Kang, Ning, Zhang, Jing-Hai, Qiu, Feng, Chen, Sheng, Tashiro, Shin-ichi, Onodera, Satoshi, Ikejima, Takashi
Format Journal Article
LanguageEnglish
Published Northbrook, IL American Chemical Society and American Society of Pharmacognosy 25.06.2010
American Society of Pharmacognosy
Subjects
Biological and medical sciences
General pharmacology
Medical sciences
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Antineoplastic agent
Human
Larynx carcinoma
Terpenoid
Cytotoxicity
In vitro
Biological activity
Medicinal plant
Cell line
Labiatae
Dicotyledones
Angiospermae
Diterpene
G2 Phase
Spermatophyta
Larynx
Mechanism of action
Antimitotic
Tumor cell
Apoptosis
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Summary: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 G2/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 (ΔΨm), 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 G2/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.
ISSN:0163-3864
1520-6025
DOI:10.1021/np9008199