Research Papers:
Antitumor and antimetastatic activities of a novel benzothiazole-2-thiol derivative in a murine model of breast cancer
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Abstract
XiaoLin Hu1,*, Sen Li2,*, Yan He3,*, Ping Ai3,*, Shaoyong Wu3,*, Yonglin Su4,*, Xiaolin Li5, Lei Cai6, Xingchen Peng3
1Department of Nursing, West China Hospital, Sichuan University, Chengdu, China
2Department of Spinal Surgery, Traditional Chinese Medicine Hospital of SouthWest Medical University, Luzhou, China
3Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
4Department of Rehabilitation, West China Hospital, Sichuan University, Chengdu, China
5Department of Pathophysiology, Basic Medical College, Jilin University, Changchun, China
6Hepatobiliary Surgery Institute, Southwest Hospital, Third Military Medical University, Chongqing, China
*These authors have contributed equally to this work
Correspondence to:
Xingchen Peng, email: [email protected]
Keywords: benzothiazole-2-thiol derivative, breast cancer, proliferation, metastasis, apoptosis
Received: November 24, 2016 Accepted: December 21, 2016 Published: January 02, 2017
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.
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