RRC ID 42346
Author Wakabayashi H, Nishishiro M, Arikawa S, Hashimoto K, Kikuchi H, Nishikawa H, Kurihara T, Terakubo S, Shoji Y, Nakashima H, Motohashi N, Sakagami H.
Title Cytotoxic activity of azulenequinones against human oral tumor cell lines.
Journal Anticancer Res
Abstract We investigated twenty-seven azulenequinone derivatives for their relative cytotoxicity against three human normal cell lines (HGF, HPC, HPLF) and four human tumor cell lines (HSG, HSC-2, HSC-3, HL-60). Parent 1,5-azulenequinone showed potent and some tumor-specific cytotoxicity. Halogenated derivatives of 1,5- and 1,7-azulenequinone showed potent cytotoxicity, but lower tumor-specific cytotoxicity. In contrast to other azulenequinones, amino derivatives such as 3-amino-1,5- and 1, 7-azulenequinones showed relatively lower cytotoxic activity. The 3-Phenoxy-1,5-azuleneqinone derivative showed higher cytotoxicity than the 3-phenoxy-1, 7-azulenequinone derivative. 1,5- and 1,7-Azulenequinones generally showed higher cytotoxicity, as compared with tropolones and azulene derivatives. 3- (3-Guaiazulenyl)-1, 5-azulenequinone [12] and 7-isopropyl-3- (4-methylanilino)-2-methyl- 1, 5-azulenequinone [24] showed a relatively higher TS value and induced apoptosis (internucleosomal DNA fragmentation, activation of caspases 3, 8 and 9) in HL-60 and HSC-2 cells, possibly via the activation of both mitochondria-independent (extrinsic) and -dependent (intrinsic) pathways. Western blot analysis showed that [24] slightly increased the intracellular concentration of pro-apoptotic proteins (Bad, Bax) in HSC-2 cells, whereas [12] was much less active. None of the twenty-seven azulenequinones showed anti-HIV activity. These results suggest [12] and [24] as possible candidates for future cancer chemotherapy.
Volume 25(1A)
Pages 305-12
Published 2005-1-1
PMID 15816552
MeSH Anti-HIV Agents / pharmacology Antineoplastic Agents / pharmacology Apoptosis / drug effects Azulenes Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cycloheptanes / pharmacology* Drug Screening Assays, Antitumor HIV Infections / drug therapy HIV-1 HL-60 Cells Humans Mouth Neoplasms / drug therapy* Mouth Neoplasms / pathology Quinones / pharmacology* Structure-Activity Relationship
IF 1.994
Times Cited 14
Human and Animal Cells HSC-2(RCB1945) HSC-3(RCB1975)