In vitro and in vivo assessments of two novel hydrazide compounds against breast cancer as well as mammary tumor cells

Mousavi, Elham; Tavakolfar, Shahrzad; Almasirad, Ali; Kooshafar, Zahra; Dehghani, Soudeh; Afsharinasab, Ahoo; Amanzadeh, Amir; Shafiee, Samira; Salimi, Mona

doi:10.1007/s00280-017-3318-5

Cited by 7 publications

(12 citation statements)

References 32 publications

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“…Matrigel basement membrane matrix was purchased from BD Biosciences (San Jose, USA). Compound B was synthesized in the medicinal chemistry research laboratory in the Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University [15, 16]. All chemicals used, if not indicated, were purchased from Merck (Darmstadt, Germany) and Sigma-Aldrich (St Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…MDA-MB-231 cells were treated with compound B (0.4 µM equivalent to 2 × IC 50–72h concentration) for 48 h and serum-starved overnight [15]. Following cell re-suspension, they were seeded into the upper wells (inserts) of the invasion chamber with serum free medium at a concentration of 1 × 10 5 cells/well.…”

Section: Methodsmentioning

confidence: 99%

“…Tumor sizes were periodically measured every 3 days. The volume of the tumor was determined using the following equation: tumor volume (mm 3 ) = (length × width 2 )/2, where the length and width are in mm [15]. Following the sacrifice of the animals, the tumors and lungs were dissected from the animals for histopathological and immunohistochemical analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Considering the aforementioned reports demonstrating the potential anticancer activity of compounds A and B (Fig. 1) [15], we selected the most effective compound (compound B ) to further investigate its anti-metastatic property in an in vivo model system. To the best our knowledge, this is the first report showing the anti-metastatic activity of this compound.

Fig.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Fig.…”

Section: Introductionmentioning

confidence: 99%

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

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“…5a). These types of cells were nominated as an invasive lineage representing a suitable model to evaluate the potency of anticancer drugs due to its similarities with metastatic human breast cancer [51]. In the groups treated with 1 mg/kg/day of the chloroform or ethyl acetate fractions, a number of tumor cells in the process of necrosis were observed (Fig.…”

Section: Resultsmentioning

confidence: 99%

Potent antitumor property of Allium bakhtiaricum extracts

Vafaee

Dehghani

Tahmasvand

et al. 2019

BMC Complement Altern Med

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Background Allium species are magnificently nutritious and are commonly used as a part of the diet in Iran. They have health enhancing benefits including anticancer properties due to the presence of numerous bioactive compounds. Herein, we investigated in vitro and in vivo anticancer properties of Allium bakhtiaricum extracts. Methods Anti-growth activity of different fractions was explored in vitro on different cancerous cells using MTT assay, Annexin V/PI and SA-β-gal staining, Western blotting, flowcytometric and immunofluorescence microscopic evaluations. In vivo antitumor activity was investigated in BALB/c mice bearing 4 T1 mammary carcinoma cells. Results We demonstrated that chloroformic and ethyl acetate fractions exert cytotoxic activity toward MDA-MB-231 cells, the most sensitive cell line, after 72 h of treatment with IC 50 values of 0.005 and 0.006 mg/ml, respectively. Incubation of MDA-MB-231 cells with ¼ and ½ IC 50-72h concentrations of each fraction resulted in a significant G2/M cell cycle arrest. ¼ IC 50-72h concentration of the chloroform fraction led to the disruption of polymerization in mitotic microtubules. Exposure of human breast cancer cells to different concentrations of the extracts at different incubation times did not induce apoptosis, autophagy or senescence. Our in vivo study revealed that administration of the chloroform extract at a dose of 1 mg/kg/day strongly suppressed mammary tumor progression and decreased the number of proliferative cells in the lung tissues indicating its anti-metastatic effect. Conclusion Our findings imply that the chloroform fraction of Allium bakhtiaricum possesses the suppressive action on breast cancer through mitotic cell cycle arrest suggesting a mechanism associated with disturbing microtubule polymerization. Electronic supplementary material The online version of this article (10.1186/s12906-019-2522-8) contains supplementary material, which is available to authorized users.

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