A novel hydrazide compound exerts anti-metastatic effect against breast cancer

Soudeh Dehghani,Mona Salimi,Raheleh Tahmasvand,Samira Shafiee,Ali Almasirad,Fariborz Moayer,Zahra Kooshafar,Ahad Muhammadnejad

doi:10.1186/s40659-019-0247-2

Abstract

BackgroundThere are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. In looking for new anticancer agents, we reported two novel hydrazide derivatives with anti-cancer activity in human breast cancer cells. The current study aims to explore the therapeutic potential of the most effective one, N'-((5-nitrothiophen-2-yl)methylene)-2-(phenylthio)benzohydrazide (compound B), on metastatic breast cancer, which is resistant to available chemotherapeutics.Methods4T1 mammary carcinoma cells were inoculated into the fat pad mammary of 5–7-week-old female BALB/c mice and then the effective compound was intraperitoneally administered for 4 weeks. Proliferation index and angiogenesis in tumor and lung tissues were examined with immunohistochemistry. In vitro assessments were also carried out to evaluate the effect of the compound on invasion of MDA-MB-231 cells.ResultsOur results demonstrated that this effective derivative significantly inhibited invasion of MDA-MB-231 cells in vitro as shown by Matrigel assay and quantitative real-time method for MMP-9 expression after 48 h of treatment. Daily administration of the compound suppressed the growth of primary tumor and its metastasis to lung, which was confirmed by H&E experiment at a dose of 1 mg/kg in a well-known metastatic model of 4T1 breast cancer in syngeneic BALB/c mice. These outcomes were supported by the immunohistochemical examinations of the tumor and lung tissues of mice. Tumors and lungs in mice treated with the effective compound showed a reduced proliferation index and a smaller microvessel density compared to the control.ConclusionThis study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer.

Highlights

There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells
Anti‐invasive properties of compound B In order to determine anchorage-independent growth and self-renewal of breast cancer cells in the presence of compound B, we applied the soft agar colony formation assay and defined as the ability of the cells to independently grow on a solid surface [19]
We treated MDA-MB-231 cells with 1.4 μM of compound A and observed that this compound caused less consequence on the invaded cells and less number of colonies in soft agar formation compared with MDA-MB-231 cells alone after 48 h (Additional file 1: Fig. S1)

Summary

Introduction

There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. Lack of a proper targeted therapy along with a resistance to chemotherapy has made this subtype of breast cancer a major concern [9] To overcome this issue, mouse mammary cancer 4T1 cell line has been used in establishing an animal model with a Dehghani et al Biol Res (2019) 52:40 high metastatic feature in BALB/c mice, recapitulating breast cancer in human body [10]. Mouse mammary cancer 4T1 cell line has been used in establishing an animal model with a Dehghani et al Biol Res (2019) 52:40 high metastatic feature in BALB/c mice, recapitulating breast cancer in human body [10] Using this murine model has become a fundamental tool for the development of chemotherapeutic agents with improved clinical trial outcomes [11]

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Discussion

Conclusion