Comparative study of the antitumor effect of natural monoterpenes: relationship to cell cycle analysis

Abstract

Abstract:Monoterpenes have been identifi ed as responsible of important therapeutic effects of plant-extracts. In this work, we try to compare the cytotoxic effect of six monoterpenes (carvacrol, thymol, carveol, carvone, eugenol and isopulegol) as well as their molecular mechanisms. The in vitro antitumor activity of the tested products, evaluated against fi ve tumor cell lines, show that the carvacrol is the most cytotoxic monoterpene. The investigation of an eventual synergistic effect of the six natural monoterpenes with two anticancer drugs revealed that there is a signifi cant synergy between them (p<5%). On the other hand, the effect of the tested products on cell cycle progression was examined by fl ow cytometry after DNA staining in order to investigate the molecular mechanism of their cytotoxic activity. The results revealed that carvacrol and carveol stopped the cell cycle progression in S phase; however, thymol and isopulegol stopped it in G0/G1 phase. Regarding carvone and eugenol, no effect on cell cycle was observed.

Antioxidant and Antiproliferative Properties of the Essential Oils of Satureja thymbra and Satureja parnassica and their Major Constituents

“…This was verified in more recent work where HepG2 cells were treated with carvacrol for 24 h (30). Carvacrol has been tested against MDA-MB 231 (human metastatic breast cancer cells) (31), P-815 (murine mastocytoma), K-562 (human chronic myelolytic leukemia), CEM (acute T-lymphoblastoid Fitsiou et al: Bioactivities of Satureja Oils and Components leukemia), MCF-7 (human breast adenocarcinoma) and its counterpart resistant to gemcitabine (MCF-7 gem) (32,33), human cervical cancer HeLa and SiHa cells (34), CEM leiomyosarcoma cells (35), B16-F10 murine melanoma cells and rat brain N2a neuroblastoma cells (36), exhibiting moderate to strong antiproliferative activity.…”

“…This sensitivity was higher than a third study dealing with the same cell line (37), perhaps due to different incubation times and cell viability assays. Finally, its effect on P-815, K-562, CEM and MCF-7 cell lines was diverse, with EC 50 values ranging from 0.15-0.48 μΜ (33).…”

Cetuximab Immunoliposomes Enhance Delivery of 5-FU to Skin Squamous Carcinoma Cells

“…[23] was used to calculate the combination index between the drugs (5-FU and cetuximab), as represented in Equation 2: $$\mathrm{normalC}\mathrm{normalI}=false({\mathrm{D}}_1/{\mathrm{D}}_{\mathrm{normalX}1}false)+false({\mathrm{D}}_2/{\mathrm{D}}_{\mathrm{normalX}2}false),$$ where D 1 and D 2 are the doses of drugs 1 and 2 necessary to produce IC50 effect in combination. D x1 and D x2 are the doses of drugs 1 and 2 necessary to produce the same effect individually, CI<1 represents synergism, CI>1 antagonism and an average CI of 1 represents additivity [24]. …”

Rapamycin-loaded Immunoliposomes Functionalized with Trastuzumab: A Strategy to Enhance Cytotoxicity to HER2-positive Breast Cancer Cells

“…The CI was calculated using the equation below: $$\mathrm{CI}:{\left(\mathrm{normalD}\right)}_1∕{\left(\mathrm{Dx}\right)}_1+{\left(\mathrm{normalD}\right)}_2∕{\left(\mathrm{Dx}\right)}_2$$ Where, (D) 1 and (D) 2 are the doses of drug 1 and drug 2 required for the IC50 effect when combined, and (D x ) 1 and (D x ) 2 represent the doses of drug 1 and drug 2 necessary to produce individual IC50. For the interpretation, CI<1 represents synergistic effect, CI>1 represents antagonism and CI equivalent to 1 represents additive effect [30]. …”