Essential Oils, Pituranthos chloranthus and Teucrium ramosissimum, Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein.

The multidrug resistance phenotype is a global phenomenon and causes chemotherapy failure in various cancers, such as in uterine sarcomas that have a high mortality rate. To overcome this phenotype, there is growing research interest in developing new treatment strategies. In this study, we highlight the potential of two essential oils from the Apiaceae family, Pituranthos chloranthus (PC) and Teucrium ramosissimum Desf. (TR), to act as chemopreventive and chemosensitizing agents against two uterine sarcoma cell lines, MES-SA and P-gp-overexpressing MES-SA/Dx5 cells. We found that PC and TR were able to inhibit the cell viability of sensitive MES-SA and resistant MES-SA/Dx5 cells by a slight modulation of the cell cycle and its regulators, but also through a significant induction of apoptosis. The molecular mechanism involved both caspase pathways associated with an overproduction of reactive oxygen species (ROS) and mitochondrial membrane depolarization. Very interestingly, the combination of doxorubicin with PC or TR induced a synergism to increase cell death in resistant MES-SA/Dx5 cells and, subsequently, had the benefit of decreasing the resistance index to doxorubicin. These synergistic effects were reinforced by a decrease in P-gp expression and its P-gp adenosine triphosphatase (ATPase) activity, which subsequently led to intracellular doxorubicin accumulation in resistant sarcoma cells.

Xanthohumol, a Prenylated Flavonoid from Hops, Induces DNA Damages in Colorectal Cancer Cells and Sensitizes SW480 Cells to the SN38 Chemotherapeutic Agent.

In spite of chemotherapy and systematic screening for people at risk, the mortality rate of colorectal cancer (CRC) remains consistently high, with 600,000 deaths per year. This low success rate in the treatment of CRC results from many failures associated with high resistance and the risk of metastasis. Therefore, in response to these therapeutic failures, new strategies have been under development for several years aimed at increasing the effect of anticancer compounds and/or at reducing their secondary effects on normal cells, thus enabling the host to better withstand chemotherapy. This study highlights that xanthohumol (Xn) concentrations under the IC50 values were able to induce apoptosis and to enhance the DNA-damage response (DDR). We demonstrate for the first time that Xn exerts its anticancer activity in models of colon cancer through activation of the ataxia telangiectasia mutated (ATM) pathway. Subsequently, the ability of Xn to restore DNA damage in CRC cells can sensitize them to anticancer agents such as SN38 (7-ethyl-10-hydroxycamptothecin) used in chemotherapy.