title: Novel therapy for locally advanced triple-negative breast cancer.
abstract: To evaluate a novel therapy for triple-negative breast cancer (TNBC), the biological responses to vitamin K3 (VK3) should be considered with the understanding of the features of breast cancer. In human breast cancer cell lines, the effects of VK3 on cell growth inhibition and the cellular signaling pathway were determined by MTT assay and western blotting. In the in vivo study, a subcutaneous tumor model of breast cancer was created, VK3 was injected into the subcutaneous tumors, and tumor size was measured. The IC50 of VK3 for breast cancer cells was calculated to be 11.3-25.1 µM. VK3 induced phosphorylation of whole tyrosine and epidermal growth factor receptor. VK3 mediated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) for 30 min. ERK but not JNK phosphorylation was maintained for at least 6 h. In contrast, another antioxidant agent, catalase, showed no effect on either ERK phosphorylation or growth inhibition. On built-up tumors under the skin of mice, local treatment with VK3 was effective in a time- and dose-dependent manner, and the experiments for total tumor volume also showed a dose-dependent effect of VK3. The expression of phosphorylated ERK was clearly detected at 10.9 times the control in tumor tissue, whereas ethanol itself showed no effect. In conclusion, ERK plays a critical role in VK3-induced growth inhibition, and it will be the focus of next steps in the development of molecular therapy for TNBC.
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Multidisciplinary Therapy for Hepato-Biliary-Pancreatic Cancer, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Osada
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanahashi
authors.affiliation: Multidisciplinary Therapy for Hepato-Biliary-Pancreatic Cancer, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsui
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Okumura
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Matsuhashi
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D064726:Triple Negative Breast Neoplasms; D024483:Vitamin K 3 / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D024483:Vitamin K 3; D048049:Extracellular Signal-Regulated MAP Kinases