Commiphora gileadensis sap extract induces cell cycle-dependent death in immortalized keratinocytes and human dermoid carcinoma

Eitan Wineman, Iain Douglas, Vanessa Wineman, Ksenia Sharova, Marcel Jaspars, Shiri Meshner, Zvi Bentwich, Guy Cohen*, Avi Shtevi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)
8 Downloads (Pure)


Commiphora gileadensis is an aromatic plant traditionally used in the Middle East as a common remedy for pain and inflammation. Recently, several studies have reported on its anti-proliferative effect in cancer cell lines. Yet, scientific evidence regarding the other properties of C. gileadensis is limited. The aim of the current study was to investigate the cytotoxic action of C gileadensis sap extracts (CgSE) on human epidermal cells and skin tissues and to ascertain its mode of action. The effects of the extract on cell viability and apoptosis were evaluated on immortalized keratinocytes, human dermal fibroblasts, human dermoid carcinoma cells and on human ex vivo skin cultures. CgSE significantly reduced the viability of both immortalized and transformed epidermal cells by 64% and 68%, respectively. However, normal fibroblasts and human skin organ cultures were protected from this effect. The cytotoxicity was coupled with the induction of capsase-3 and the morphological characteristics of apoptosis. In addition, CgSE-induced apoptosis did not occur in cells in the pre-replicative, G(1) phase, but only at later phases involved in DNA replication and cell division. HPLC analysis of CgSE showed only negligible traces of beta-caryophyllene, a secondary metabolite previously isolated from C gileadensis and reported to be cytotoxic. Therefore, additional active compound(s) may be involved in the anti-proliferative phenomenon of the extract. The authors concluded that CgSE contains cytotoxic products which specifically target proliferating cells in a cell cycle-dependent manner, and hence may be relevant for the treatment of skin disorders characterized by hyperproliferation, such as skin cancer and psoriasis. (C) 2015 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (

Original languageEnglish
Pages (from-to)199-206
Number of pages8
JournalJournal of herbal medicine
Issue number4
Early online date3 Sept 2015
Publication statusPublished - Dec 2015

Bibliographical note

We would like to dedicate this article to the memory of Professor Yoram Milner, who has passed away before this study was achieved. We are immeasurably indebted to him, professionally and personally. The study was supported by grants from the ICA Foundation and the Ministry of Science, Technology and Space.


  • Commiphora gileadensis
  • Skin disorders
  • Cell cycle
  • Apoptosis
  • Oxidative stress
  • Saudi-Arabia
  • Human Skin
  • Opobalsamum
  • Cancer
  • Guggulsterone
  • Antioxidant
  • Activation
  • Arrest


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