title: DMNQ S-64 induces apoptosis via caspase activation and cyclooxygenase-2 inhibition in human nonsmall lung cancer cells.
abstract: Shikonin has been reported to induce apoptosis and inhibit angiogenesis in vivo and in vitro. 6-(1-propoxyiminoalkyl)-5,8-dimethoxyoxy 1,4-naphtoquinone S-64 (DMNQ S-64) was synthesized as a shikonin derivative. In this article, the underlying apoptotic mechanism of DMNQ S-64 was examined. DMNQ S-64 exerted cytotoxicity against A549 lung carcinoma cells with IC(50) of 27.3 microM. Apoptotic bodies were observed in DMNQ S-64-treated A549 cells by 4'-6-diamidino-2-phenylindole (DAPI) staining assay. DMNQ S-64 also increased sub-G1 DNA portion in a concentration-dependent manner by flow cytometric analysis. Western blotting has revealed that DMNQ S-64 effectively activates the expression of caspase 8, 9, and 3, cleaves poly (ADP-ribose) polymerase, and increases the ratio of Bax/Bcl-2. Furthermore, cytochrome c was released in a concentration-dependent manner by DMNQ S-64. Similarly, DMNQ S-64 significantly increased caspase 3 activity by enzyme-linked immunosorbent assay (ELISA). It also significantly inhibited the level of prostaglandin E2 (PGE(2)) by ELISA and downregulated the expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner. Taken together, DMNQ S-64 may exhibit cytotoxicity against A549 cells via caspase activation and COX-2 inhibition.
authors.affiliation: O.Lab of Angiogenesis and Chemoprevention, College of Oriental Medicine, Kyunghee University, 1 Hoegi-dong, Dongdaemun-ku, Seoul 131-701, South Korea.
authors.forename: Eu-Soo
authors.initials: ES
authors.lastname: Lim
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Rhee
authors.forename: Min-Kyu
authors.initials: MK
authors.lastname: Park
authors.forename: Beom-Sang
authors.initials: BS
authors.lastname: Shim
authors.forename: Kyoo-Seok
authors.initials: KS
authors.lastname: Ahn
authors.forename: Hee
authors.initials: H
authors.lastname: Kang
authors.forename: Hwa-Seung
authors.initials: HS
authors.lastname: Yoo
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006898:Hydroxylamines / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D009285:Naphthoquinones / Q000494:pharmacology*
chemical_list: C519381:6-(1-propoxyiminoalkyl)-5,8-dimethoxy-1,4-naphthoquinone S-64; D000972:Antineoplastic Agents, Phytogenic; D052246:Cyclooxygenase 2 Inhibitors; D006898:Hydroxylamines; D008565:Membrane Proteins; D009285:Naphthoquinones; C016101:shikonin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020169:Caspases