title: Andrographolide inhibits oral squamous cell carcinogenesis through NF-κB inactivation.
abstract: The NF-κB family of transcription factors is essential for promoting cell proliferation and preventing cell apoptosis. We have previously shown that Andrographolide (Andro) isolated from an herbal plant, Andrographis paniculata, covalently modifies reduced cysteine(62) in the oligonucleotide binding pocket of p50 for inhibition of NF-κB activation. Here we report that Andro, but not its inactive structural analog 4H-Andro, potently suppressed squamous cell carcinogenesis induced by 7,12-dimethyl-1,2-benzanthracene (DMBA) in the hamster model of cheek buccal pouch. Compared with 4H-Andro, Andro reduced phosphorylation of p65 (Ser536) and IκBα (Ser32/36) for inhibiting aberrant NF-κB activation, suppressed c-Myc and cyclin D1 expression and attenuated neoplastic cell proliferation, promoted cancerous cell apoptosis, and mitigated tumor-induced angiogenesis. Consistently, Andro retarded growth, decreased proliferation, and promoted apoptosis of Tb cells, a human tongue squamous cell carcinoma cell line, in time- and dose-dependent manners, with concomitant reduction of the expression of NF-κB targeting molecules in vitro. Our results thus demonstrate that NF-κB activation plays important roles in the pathogenesis of chemically induced squamous cell carcinoma. By inhibition of aberrant NF-κB activation, Andro treats chemically induced oral squamous cell carcinogenesis.
authors.affiliation: Vascular Biology Research Institute, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China. wanglijing62@yahoo.com.cn
authors.forename: L-J
authors.initials: LJ
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Tang
authors.forename: C-L
authors.initials: CL
authors.lastname: Qi
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Lin
authors.forename: J-T
authors.initials: JT
authors.lastname: Wang
authors.forename: J-G
authors.initials: JG
authors.lastname: Geng
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002610:Cheek; D006224:Cricetinae; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology*; D009389:Neovascularization, Pathologic; D010766:Phosphorylation / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1; C030419:andrographolide; D015127:9,10-Dimethyl-1,2-benzanthracene; D019892:eIF-2 Kinase; D051550:I-kappa B Kinase