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

Abstract

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.

Calocedrus formosana Essential Oils Induce ROS-Mediated Autophagy and Apoptosis by Targeting SIRT1 in Colon Cancer Cells

“…Moreover, studies have shown that doxorubicin in combination with Pituranthos chloranthus (PC) EO or Teucrium ramosissimum Desf. (TR) induces a synergistic effect in MES-SA/Dx5 cells and reduces the resistance index [ 58 ]. Al-Otaibi et al showed that the combination of Teucrium polium L. essential oil nanoemulsion and oxaliplatin had a synergistic effect with different p53 status colon cancer cells and induced a greater percentage of apoptosis [ 59 ].…”

Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells

“…Specifically, several EOs and their components are reported to exert anti-proliferative effects and induce apoptosis in cancer cells with minimal effects on non-transformed ones [ 27 , 28 ]. Moreover, since some of them work synergistically with commonly used anticancer drugs, they have been proposed as adjuvants in chemotherapy [ 20 , 21 , 22 ].…”

“…They have been recognized as sources of many bioactive products that exhibit various biological and immunological activities, including anti-inflammatory, antibacterial, antibiofilm, antifungal and antiviral effects [ 16 , 17 , 18 , 19 ]. Furthermore, EOs have been shown to exert cancer cell targeting activity to increase the efficacy of commonly used chemotherapy drugs and to possess pro-immune functions [ 20 , 21 , 22 , 23 ]. Despite a large body of research indicating that EOs and their active compounds may have anticancer properties, not many successful drug formulations have reached the clinical stage.…”

Teucrium ramosissimum Derived-Natural Products and Its Potent Effect in Alleviating the Pathological Kidney Damage in LPS-Induced Mice

“…Moreover, Teucrium extract exert different protective effects against ethanol-induced ulcerogenesis [14]. Likewise, this species acts as chemopreventive and chemosensitizing agent against two uterine sarcoma cell lines, MES-SA and P-gp-overexpressing MES-SA/ Dx5 cells by a slight modulation of the cell cycle and its regulators, but also through a significant induction of apoptosis [15].…”