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

Abstract

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.

The effect of chlorophyllin, a glutathione transferase P1‐1 inhibitor, on triple-negative breast cancer invasion and metastasis in vivo/in vitro

“…Although both docetaxel and chlorophyllin could inhibit cell migration alone, their combined treatment had a substantially stronger effect. There was no available study in literature investigating the effects of combined use of chlorophyllin with anticancer drugs on cell migration, however, these results were in line with other studies reporting that certain antioxidants and/or phytochemicals administration, such as chlorophyllin, reduced the cell migration in aggressive cancer cell lines (Lirdprapamongkol, Sakurai et al 2005, Roomi, Bhanap et al 2018, Dehghani, Kooshafar et al 2019). In a study on HT-1080 brosarcoma cells, it was shown that chlorophyllin dose-dependently reduced the cell migration, and this effect was highest at 50 µM chlorophyllin administration (Roomi, Bhanap et al 2018).…”

In silico predictions on the possible mechanism of action of selected bioactive compounds against breast cancer

“…Molecular subtyping has identified three distinct histological types of breast cancer: hormone receptor (HR) positive, human epidermal growth factor receptor (HER2/neu) positive, and triple-negative (TN) (Kumar et al 2019). Triple-negative breast cancer is characterized by high invasiveness, poor prognosis and frequent relapse following treatment (Dehghani et al 2019). Triplenegative breast cancer lacks progesterone (PR), estrogen (ER) and HER2 receptor expression and the phenotype is associated with metastasis, lower survival rate and shorter life expectancy (Budzik et al 2019).…”

Development of the potential synthesized compound to cause triple negative breast cancer cell death through intrinsic apoptosis mechanism

“…Among several animal models, syngeneic model is reported as the most common one to study potential of drugs against breast cancer [38]. Remarkably, this model is also a suitable model for studying the antimetastatic effect in triple-negative breast cancer [39]. Thus, it was also interesting for us to know whether this compound can modulate 4T1 cells-induced metastasis in the animals.…”