Cytotoxic effect of Montivipera bornmuelleri's venom on cancer cell lines: in vitro and in vivo studies

Carol Haddoub; Mohamad Rima; Sandrine Heurtebise; Myriam Lawand; Dania Jundi; Riyad Sadek; Sebastian Amigorena; Ziad Fajloun; Marc C Karam

doi:10.7717/peerj.9909

Cytotoxic effect of Montivipera bornmuelleri's venom on cancer cell lines: in vitro and in vivo studies

PeerJ. 2020 Oct 27:8:e9909. doi: 10.7717/peerj.9909. eCollection 2020.

Authors

Carol Haddoub^#¹, Mohamad Rima^#², Sandrine Heurtebise³, Myriam Lawand³, Dania Jundi^{4

5}, Riyad Sadek⁶, Sebastian Amigorena³, Ziad Fajloun^{4

7}, Marc C Karam¹

Affiliations

¹ Department of Biology, University of Balamand, Kalhat, Al-Kurah, Lebanon.
² Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM, CNRS, University of Strasbourg, Strasbourg, France.
³ Institut Curie, INSERM U932, PSL Research University, Paris, France.
⁴ LAB3B, Doctoral School for Sciences and Technology, Azm Centre for Research in Biotechnology, Lebanese University, Tripoli, Lebanon.
⁵ Department of Neuroscience, Institute of Biology Paris-Seine (IBPS), INSERM, CNRS, Université Sorbonne-Nouvelle (Paris III), Paris, France.
⁶ Department of Biology, American University of Beirut, Beirut, Lebanon.
⁷ Faculty of Sciences 3, Michel Slayman Tripoli Campus, Lebanese University, Tripoli, Lebanon.

^# Contributed equally.

Abstract

Background: Montivipera bornmuelleri's venom has shown immunomodulation of cytokines release in mice and selective cytotoxicity on cancer cells in a dose-dependent manner, highlighting an anticancer potential. Here, we extend these findings by elucidating the sensitivity of murine B16 skin melanoma and 3-MCA-induced murine fibrosarcoma cell lines to M. bornmuelleri's venom and its effect on tumor growth in vivo.

Methods: The toxicity of the venom on B16 and MCA cells was assessed using flow cytometry and xCELLigence assays. For in vivo testing, tumor growth was followed in mice after intratumoral venom injection.

Results: The venom toxicity showed a dose-dependent cell death on both B16 and MCA cells. Interestingly, overexpression of ovalbumin increased the sensitivity of the cells to the venom. However, the venom was not able to eradicate induced-tumor growth when injected at 100 µg/kg. Our study demonstrates a cytotoxic effect of M. bornmuelleri's venom in vitro which, however, does not translate to an anticancer action in vivo.

Keywords: Anti-cancer activity; B16 cells; In vivo; MCA cells; Montivipera bornmuelleri.

Grants and funding

This work was supported by the Lebanese University, UOB and Curie Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.