Phytochemical Analysis and Cytotoxicity Towards Multidrug-Resistant Leukemia Cells of Essential Oils Derived from Lebanese Medicinal Plants

Abstract

Juniperus excelsa fruit essential oil as well as J. oxycedrus, Cedrus libani, and Pinus pinea wood essential oils have been obtained with yields between 2.2 ± 0.3 % to 3.4 ± 0.5 % and analyzed by gas chromatography. Sesquiterpenes mainly characterized C. libani and J. oxycedrus essential oils, while in P. pinea and J. excelsa, monoterpenes were the most abundant compounds. In J. oxycedrus, cis-calamenene (7.8 %), cuparene (3.8 %), and cis-thujopsenal (2.0 %) have been detected for the first time. The cytotoxic activity of these essential oils against drug-sensitive CCRF-CEM and multidrug-resistant P-glycoprotein-expressing CEM/ADR5000 leukemia cells has been investigated (IC₅₀ values: 29.46 to 61.54 µg/mL). Remarkably, multidrug-resistant CEM/ADR5000 cells did not reveal cross-resistance, indicating that these essential oils might be useful to treat otherwise drug-resistant and refractory tumors.

Evaluation of the cytotoxic effects of Cyperus longus extract, fractions and its essential oil on the PC3 and MCF7 cancer cell lines

“…β-himachalene (10.81%), α-caryophyllene oxide (7.6%), irisone (4.78%), β-caryophyllene oxide (4.36%), humulene oxide (12%), viridiflorol (4.73%), aristolone (6.39%) and longiverbenone (6.04%) were identified as the major constituents of the EO. As we already mentioned, β-himachalene ( 22 ), caryophyllene oxide ( 25 ) and α-humulene ( 20 , 21 ) have been shown to exert cytotoxic effects against cancer cell lines. The evaluation of the chemical composition of Cyperus longus EO from Morocco by the same method (GC-MS analysis) revealed a different spectrum of ingredients: α-humulene (16.7%), γ-himachalene (10.1%) and β-himachalene (46.6%) ( 31 ); however, as we have already mentioned, these agents also possess a satisfactory cytotoxic activity.…”

“…Several anticancer drugs, such as vincristine, etoposide, vinblastine, irinotecan, paclitaxel (taxol) and topotecan are botanical secondary metabolites or semi-synthetic derivatives ( 1 ). Apigenin ( 2 ), deguelin ( 3 ), kaempferol ( 4 ), luteolin ( 5 – 7 ), quercetin ( 8 – 11 ), rutin ( 12 – 16 ), tricin ( 17 ), xanthomicrol ( 18 ), α-copaene ( 19 ), α-humulene ( 20 , 21 ) and β-himachalene ( 22 ) are some botanical ingedients that have been investigated as possible future remedies for use in chemotherapy. Xanthomicrol and calycopterin have also been shown to exert potent inhibitory effects on microvessel outgrowth and that these anti-angiogenic effects enhance the antitumor activity ( 18 ).…”

P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review

“…Finally, the literature found regarding the P-gp inhibition by natural products was too much to be covered in one review article, therefore the current review focused only on major classes of naturally occurring compounds. However, several reports were found concerning the activity of various plant extracts [118] and their constituents as P-gp inhibitors; viz., anthraquinones [119] , phenylbutanoids [120] , phytosterols [121] , cannabinoids [122] , carotenoids [123] , curcumenoids [124] , volatile oils [125] , sulfur compounds [126] , and polyacetylenes. [127] In addition, some vitamins such as vitamin D revealed significant reversal of multi-drug resistance in many resistant cells [128] .…”

Essential Oils and Their Constituents as Anticancer Agents: A Mechanistic View

“…EOs of thyme are effective against widely used drugs like Adriamycin, Vincristine, and Cisplatin resistant ovarian cancer cell lines and, in addition, tumour size reduction was also observed in vivo which indicates the efficacy of the EO in mammalian system [96, 97]. Juniperus excels EO was effective against MDR P-glycoprotein-expressing CEM/ADR5000 leukemia cells and reversed their resistance indicating the use of EO in MDR treatment in cancer [98]. Melaleuca alternifolia , tea tree oil, can ameliorate Adriamycin resistance in human melanoma cells and terpinen-1-ol is responsible for this activity [99].…”