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

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, G₁ phase, but only at later phases involved in DNA replication and cell division. HPLC analysis of CgSE showed only negligible traces of β-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.