phenanthrenes and Laryngeal-Neoplasms

Triptolide, an active compound extracted from Chinese herb Leigongteng (Tripterygium wilfordii Hook F.), shows a broad-spectrum of anticancer activity through its cytotoxicity. However, the efficacy of triptolide on laryngocarcinoma rarely been evaluated, and the mechanism by which triptolide-induced cellular apoptosis is still not well understood. In this study, we found that triptolide significantly inhibited the laryngocarcinoma HEp-2 cells proliferation, migration and survivability. Triptolide induces HEp-2 cell cycle arrest at the G1 phase and apoptosis through intrinsic and extrinsic pathways since both caspase-8 and -9 are activated. Moreover, triptolide enhances p53 expression by increasing its stability via down-regulation of E6 and E6AP. Increased p53 transactivates down-stream target genes to initiate apoptosis. In addition, we found that short time treatment with triptolide induced DNA damage, which was consistent with the increase in p53. Furthermore, the cytotoxicity of triptolide is decreased by p53 knockdown or use of caspases inhibitor. In conclusion, our results demonstrated that triptolide inhibits cell proliferation and induces apoptosis in laryngocarcinoma cells by enhancing p53 expression and activating p53 functions through induction of DNA damage and suppression of E6 mediated p53 degradation. These studies indicate that triptolide is a potential anti-laryngocarcinoma drug.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Diterpenes; Epoxy Compounds; Humans; Laryngeal Neoplasms; Oncogene Proteins, Viral; Phenanthrenes; Tumor Suppressor Protein p53

Fifteen tanshinone analogues isolated from the chloroform extract of Danshen roots (Salviae Miltiorrhizae Radix) by chromatographic procedures were tested for their cytotoxic activities against KB, Hela, Colo-205 and Hep-2 carcinoma cell lines. Several of them were effective at concentrations below 1 micrograms/ml concentrations. Tanshinone analogues with either hydroxy substitutions or olefinic feature in ring A demonstrated higher biologic activities. Analysis of structure-activity relationship indicate that the basic requirement for activity is the presence of a furano-o-naphthoquinone in the molecule. Compounds which lack an intact furan ring were found to be inactive. It is suggested that the planar phenanthrene ring of the tanshinones may be essential for interaction with DNA molecule whereas the furano-o-quinone moiety could be responsible for the production of reactive free radicals in the close vicinity of the bases to cause DNA damage.

Topics: Abietanes; Anti-Infective Agents; Carcinoma; Colonic Neoplasms; Drug Screening Assays, Antitumor; HeLa Cells; Humans; KB Cells; Laryngeal Neoplasms; Lethal Dose 50; Phenanthrenes; Tumor Cells, Cultured