Antitumor and antimetastatic activities of a novel benzothiazole-2-thiol derivative in a murine model of breast cancer

XiaoLin Hu; Sen Li; Yan He; Ping Ai; Shaoyong Wu; Yonglin Su; Xiaolin Li; Lei Cai; Xingchen Peng

doi:10.18632/oncotarget.14431

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Research Papers:

Antitumor and antimetastatic activities of a novel benzothiazole-2-thiol derivative in a murine model of breast cancer

XiaoLin Hu _, Sen Li, Yan He, Ping Ai, Shaoyong Wu, Yonglin Su, Xiaolin Li, Lei Cai and Xingchen Peng

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Oncotarget. 2017; 8:11887-11895. https://doi.org/10.18632/oncotarget.14431

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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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Research Papers:

Antitumor and antimetastatic activities of a novel benzothiazole-2-thiol derivative in a murine model of breast cancer

Abstract