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

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Abstract

Purpose

The hydrazide backbone is a well-known structural core system found in a broad range of biologically activated compounds. Among which, the compounds with anticancer activity have been cited in a number of studies. With this object in mind, we focused on the in vitro and in vivo anticancer potential of two novel hydrazide derivatives bearing furan or thiophen substituents (compounds 1 and 2).

Methods

The cytotoxic property was evaluated using MTT assay against MCF-7 human breast adenocarcinoma cell line, while the in vivo antitumor activity was investigated in BALB/c mice bearing 4T1 mammary carcinoma cells. Flow cytometry was used for cell cycle analysis, and detection of apoptosis was examined by Annexin-V-FLUOS/PI assay. Protein expression of Bax, Bcl-2 and procaspase-3 was estimated by Western blotting.

Results

Compounds 1 and 2 were found to be cytotoxic towards breast cancer cells presenting IC50 values of 0.7 and 0.18 µM, respectively, and selectivity over normal fibroblast cells. Our findings further indicated that 2 × IC50 concentrations of both compounds induce early stage apoptosis and increase percentage of sub-G1 population in MCF-7 cells at 48 h. An elevation in Bax/Bcl-2 ratio and caspase-3 cleavage suggested that apoptosis induced by the two compounds is through a caspase- and mitochondrial-dependent pathway. In the in vivo study, compounds 1 and 2 at doses of 10 and 1 mg/Kg/day, respectively, significantly hindered the growth of tumor after 3 weeks of i.p. administration, when compared to vehicle-treated mice.

Conclusion

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

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Author information

Author notes

  1. Zahra Kooshafar and Soudeh Dehghani contributed equally to this work.

Authors and Affiliations

  1. Department of Biology, Science and Research Branch Islamic Azad University, Tehran, Iran

    Elham Mousavi & Shahrzad Tavakolfar

  2. Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran

    Ali Almasirad & Samira Shafiee

  3. Department of Biology, Engineering and Science Faculty, Science and Art University, Yazd, Iran

    Zahra Kooshafar & Soudeh Dehghani

  4. Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, P.O. Box 13164, Iran

    Ahoo Afsharinasab & Mona Salimi

  5. National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran

    Amir Amanzadeh

Authors
  1. Elham Mousavi
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  2. Shahrzad Tavakolfar
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  3. Ali Almasirad
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  9. Mona Salimi
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Corresponding author

Correspondence to Mona Salimi.

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Funding

This research was financially supported by Pasteur Institute of Iran.

Conflict of interest

The authors have declared that there is no conflict of interests to disclose.

Ethical approval

All applicable national and institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Mousavi, E., Tavakolfar, S., Almasirad, A. et al. In vitro and in vivo assessments of two novel hydrazide compounds against breast cancer as well as mammary tumor cells. Cancer Chemother Pharmacol 79, 1195–1203 (2017). https://doi.org/10.1007/s00280-017-3318-5

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  • DOI: https://doi.org/10.1007/s00280-017-3318-5

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