title: In Vitro and in Vivo Anticancer Activity of Pardaxin against Proliferation and Growth of Oral Squamous Cell Carcinoma.
abstract: Pardaxin (H-GFFALIPKIISSPLFKTLLSAVGSALSSSGGQE-OH), a 33-amino-acid polypeptide, is an antimicrobial peptide (AMP) isolated from the marine fish species Pardachirus marmoratus. Pardaxin shows antibacterial and antitumor activities. However, pardaxin-induced inhibition of oral cancer and the mechanism of tumor reduction in buccal pouch carcinogenesis after pardaxin painting remain undetermined. Additionally, the toxic effects of pardaxin on normal tissue remain unclear. The present study investigated the anticancer activity of pardaxin in oral squamous cell carcinoma (OSCC) cells in the hamster buccal pouch model with or without 7,12-dimethylbenz[a]anthracene (DMBA) pretreatment. This is the first study to confirm the effects of pardaxin on normal tissue and its nontoxic effects in vivo. Cell viability assays and colony formation tests in OSCC cell lines (SCC-4) demonstrated that pardaxin reduced cell viability in a dose-dependent manner. Immunofluorescence staining of cleaved caspase-3 in SCC-4 cells revealed that expression of activated caspase-3 in SCC-4 cells significantly increased after 24-h treatment with pardaxin. Additionally, a cell cycle analysis indicated that pardaxin treatment resulted in the cell cycle arrest of SCC-4 cells in the G2/M phase, thereby limiting cell proliferation. Furthermore, pardaxin treatment substantially alleviated carcinogenesis in the DMBA-induced hamster buccal pouch model by lowering prostaglandin E₂ levels. These results suggest that pardaxin is a potential marine drug for adjuvant chemotherapy for human OSCC and oral cancer.
authors.affiliation: Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200000, China. yifanhan2014@gmail.com.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA. cuizhibin1985@gmail.com.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. li4094@gmail.com.
authors.forename: Yen-Hsing
authors.initials: YH
authors.lastname: Li
authors.affiliation: Biochemical Process Technology Department, Center of Excellence for Drug Development, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Rm. 103, Bldg. 27, 321, Sec. 2, Kuang Fu Rd., Hsinchu 100401, Taiwan. d99b22003@ntu.edu.tw.
authors.forename: Wei-Hsuan
authors.initials: WH
authors.lastname: Hsu
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan. f96b47117@ntu.edu.tw.|Department of Traditional Chinese Medicine, Taipei Medical University Hospital, No.252, Wu Hsing Street, Taipei 110, Taiwan. f96b47117@ntu.edu.tw.
authors.forename: Bao-Hong
authors.initials: BH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D045744:Cell Line, Tumor / Q000187:drug effects; D006224:Cricetinae; D004195:Disease Models, Animal; D005397:Fish Venoms / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009062:Mouth Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D005397:Fish Venoms; C017603:pardaxin
keywords: 7,12-dimethylbenz[a]anthracene (DMBA); antimicrobial peptide (AMP); oral cancer; oral squamous cell carcinoma (OSCC) cells; pardaxin