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Cupressus sempervirens extract inhibited human basal cell carcinoma tumorigenesis, local invasion, and angiogenic property

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Abstract

Basal cell carcinoma, a noninvasive and rarely metastatic tumor, correlates with clinical and histological involvement of basal epithelial cells. It occurs due to dysregulation of hedgehog-patched1 signaling pathway. The current study was conducted to evaluate the in vitro cytotoxic effects of Cupressus sempervirens methanolic extract against primary basal cell carcinoma cells, over a period of 48 h. We measured protein level of Annexin-V and the leakage rate of lactate dehydrogenase in cells being exposed to 420 μM extract. In addition to transcript levels of PTCH-1, a receptor of  of hedgehog signaling pathway, angiogenic activity of tumor cells were determined in terms of the amount of vascular endothelial growth factor and angiopoietin-2, and metastatic levels of matrix metalloproteinase 2 and 9.

The cytotoxicity test results showed that BCC cells survival decreased dose-dependently over 48 h after exposure to plant extract. The expression of Annexin-V was induced (p < 0.05) in treated cells which coincided with raised levels of lactate dehydrogenase in supernatant media (p < 0.05). Noticeably, the expression of PTCH-1, vascular endothelial growth factor, angiopoietin-2, and matrix metalloproteinase 2 and 9 were robustly decreased. Interestingly, 6-month clinical trial follow-up of C. sempervirens extract 5% ointment showed antitumor activity against cutaneous basal cell carcinoma by the reduction of tumor and inflammatory cells replaced with fibrotic stroma. The data of present experiment may suggest that the methanolic extracts of C. sempervirens possess oncostatic and cytotoxic properties, and therefore, can be prescribed as natural protective and therapeutic ingredients for basal cell associate cutaneous tumor.

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Acknowledgements

The current experiment was financially supported by a grant from the Tabriz University of Medical Sciences. We kindly thank Mr. Nasseri for technical support in preparation of plant extract and Dr. Talghini for histopathological confirmation.

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Authors and Affiliations

  1. Department of Dermatology, Tabriz University of Medical Sciences, Sina Hospital, Azadi St, Tabriz, 5163639888, Iran

    Mehdi Amirnia, Fatemeh Mokhtari, Effat Khodaiani & Anali Sadeghi

  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Aysa Rezabakhsh

  3. Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, 5166614756, Iran

    Aysa Rezabakhsh, Elaheh Nabat, Sajad Khalilzadeh & Reza Rahbarghazi

  4. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Ali Akbar Movassaghpour

  5. Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Abbas Delazar

  6. Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Reza Rahbarghazi

Authors
  1. Mehdi Amirnia
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  2. Fatemeh Mokhtari
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  3. Aysa Rezabakhsh
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  6. Sajad Khalilzadeh
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  7. Ali Akbar Movassaghpour
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  8. Abbas Delazar
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  9. Anali Sadeghi
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  10. Reza Rahbarghazi
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Corresponding authors

Correspondence to Fatemeh Mokhtari or Reza Rahbarghazi.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Funding sources

This study was supported by research grant from the Tabriz University of Medical Sciences.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Fatemeh Mokhtari and Reza Rahbarghazi contributed equally to this work.

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Amirnia, M., Mokhtari, F., Rezabakhsh, A. et al. Cupressus sempervirens extract inhibited human basal cell carcinoma tumorigenesis, local invasion, and angiogenic property. Comp Clin Pathol 26, 203–211 (2017). https://doi.org/10.1007/s00580-016-2370-6

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  • DOI: https://doi.org/10.1007/s00580-016-2370-6

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