No abstract

Collectively, the great potential exhibited by compound 2 could make it a promising chemotherapeutic candidate for human cancers, especially for breast cancer.

Background There 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. Methods 4T1 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. Results Our 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. Conclusion This study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer. Electronic supplementary material The online version of this article (10.1186/s40659-019-0247-2) contains supplementary material, which is available to authorized users.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome, and currently no effective targeted therapies are available. Since cancer develops owing to deregulation of apoptosis, employing therapeutic strategies with ability to target the molecules involved in apoptosis induction, would provide a valid approach to hinder tumor progression. Hydrazide-hydrazones and oxamide molecules are the subject of intense studies due to their anticancer effects via apoptosis induction. In the present study, we attempted to elucidate the mechanism of action of a synthesized compound (compound A) and understand if the cell death occurs through inducing the apoptosis. These properties were investigated using the, annexin/PI and Western blotting analyses, DAPI staining, and mitochondrial membrane potential probe. Compound A also impeded the tumor growth in a 4T1 syngeneic mouse model as evidenced by hematoxylin and eosin staining of the tumors. Apart from that, it significantly diminished the expression of pro-caspase-3, Ki67 and CD31 markers in the tumor sections. Conclusively, this study for the first time reports the anti-cancer efficacy of compound A in both in vitro and in vivo models, which may serve as a potent candidate in triple negative breast cancer (TNBC) treatment.