In Vitro and In Vivo Evaluation of the Anticancer and Anti-inflammatory Activities of 2-Himachelen-7-ol isolated from Cedrus Libani

Andree Elias,Nahia Dib-Jalbout,Wissam Faour,Mohamad Mroueh,Robin I Taleb,Bilal Nehme,Rita Iskandar,Wassim N Shebaby,Costantine Daher,Bassem S Bassil,Joelle El Hakim

doi:10.1038/s41598-019-49374-9

Andree Elias, Nahia Dib-Jalbout + Show 9 more

Open Access

https://doi.org/10.1038/s41598-019-49374-9

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Abstract

Cedrus libani is a majestic evergreen tree native to the Mediterranean mountains of Lebanon, Syria and Turkey. In this study, the tree heart wood was extracted using hexane to produce C. libani oil extract (CLOE) as a dark oil. GCMS analysis of CLOE identified up to 30 compounds whereby 2-himachalen-7-ol (7-HC) was the most abundant (40%). 7-HC was isolated using column chromatography and the identity of the white crystalline solid was confirmed via NMR spectroscopy and X-Ray Crystallography. 7-HC demonstrated potent cytotoxic activity against several human cancer cell lines including brain (SF-268, IC50 8.1 μg/mL) and colon (HT-29, IC50 10.1 μg/mL; Caco-2, IC50 9.9 μg/mL) with ovarian (Sk-OV-3, IC50 > 50 μg/mL) cells being the most resistant. However, while HT-29 displayed resistance to Cisplatin, 7-HC was 8–10 folds more potent. Co-treatment with 7-HC and Cisplatin showed a significant synergistic anti-proliferative effect against SF-268, HT-29 and Caco-2 cells. 7-HC also exhibited significant anti-inflammatory effect in formalin-induced paw edema in rats. Western blot analysis revealed that 7-HC displayed dose dependent inhibition of LPS-induced COX-2 protein expression in isolated rat monocytes. The present study demonstrates that 7-HC possesses promising anticancer and anti-inflammatory activities, and may serve as a lead molecule in cancer therapy.

Highlights

The Lebanese Cedar (Cedrus libani, C. libani) is a conifer species native to the Mediterranean mountains of Lebanon and Syria as well as the Toros Mountains of Turkey[3]
Inhibition of inducible COX-218 by non-steroidal anti-inflammatory drugs caused a decrease in angiogenesis, their use can lead to inhibition of tumor progression and metastasis[19]
GCMS analysis of C. libani oil extract (CLOE) (Table 1) identified 30 compounds constituting around 83% of the oil extract with the remaining 17% constituting several unidentified compounds whereby none were found to be present in excess of 2%

Summary

Introduction

The Lebanese Cedar (Cedrus libani, C. libani) is a conifer species native to the Mediterranean mountains of Lebanon and Syria as well as the Toros Mountains of Turkey[3]. Phytochemical analysis of oils extracted from several Cedrus species revealed that steroids, procyanidins and terpenoids are the major constituents[5,6] These phytochemicals have been shown to possess a wide range of biological activities, such as anticancer[7], anti-inflammatory[8] and antimicrobial effects[9]. Inhibition of inducible COX-218 by non-steroidal anti-inflammatory drugs caused a decrease in angiogenesis, their use can lead to inhibition of tumor progression and metastasis[19]. Steroids and non-steroidal anti-inflammatory drugs are considered effective medications for prevention of ischemic events and treatment of pain, fever and inflammation. These drugs are associated with a significant risk of developing gastrointestinal or cardiovascular complications[20]. The present study aims to isolate 7-HC and investigate its anticancer activity on various cancer cell lines as well as assess its in vivo and in vitro anti-inflammatory properties

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