title: Antitumor and antimetastatic activities of a novel benzothiazole-2-thiol derivative in a murine model of breast cancer.
abstract: The prognosis of metastatic breast cancer is always very poor. Thus, it is urgent to develop novel drugs with less toxicity against metastatic breast cancer. A new drug (XC-591) derived from benzothiazole-2-thiol was designed and synthesized in our lab. In this study, we tried to assess effects of XC-591 treatment on primary breast cancer and pulmonary metastasis in 4T1 mice model. Furthermore, we tried to discover its possible molecular mechanism of action. MTT experiment showed XC-591 had significant anti-cancer activity on diverse cancer cells. Furthermore, XC-591 significantly suppressed the proliferation of 4T1 cells by colony formation assay. The in vivo results displayed that XC-591 could inhibit the growth and metastasis in 4T1 model. Moreover, histological analysis revealed that XC-591 treatment increased apoptosis, inhibited proliferation and angiogenesis in vivo. In addition, XC-591 did not contribute to obvious drug associated toxicity during the whole study. Molecular mechanism showed XC-591 could inhibit RhoGDI, activate caspase-3 and decrease phosphorylated Akt. The present data may be important to further explore this kind of new small-molecule inhibitor.
authors.affiliation: Department of Nursing, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: XiaoLin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Spinal Surgery, Traditional Chinese Medicine Hospital of SouthWest Medical University, Luzhou, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ai
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Shaoyong
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Rehabilitation, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Pathophysiology, Basic Medical College, Jilin University, Changchun, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Hepatobiliary Surgery Institute, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xingchen
authors.initials: X
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011897:Random Allocation; D013438:Sulfhydryl Compounds / Q000494:pharmacology
chemical_list: D052160:Benzothiazoles; D013438:Sulfhydryl Compounds
keywords: apoptosis; benzothiazole-2-thiol derivative; breast cancer; metastasis; proliferation