Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review

Abstract

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells’ sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene reverses tumor resistance include inhibiting the efflux of ATP binding cassette subfamily B member 1(ABCB1) transporter, reducing the transmission of exosomes, inducing apoptosis and autophagy, regulating the expression of key genes and proteins in various signaling pathways, blocking the cell cycle, inhibiting stemness, epithelial–mesenchymal transition, and so on. In this paper, the mechanisms of elemene’s reversal of drug resistance are comprehensively reviewed.

The updated role of exosomal proteins in the diagnosis, prognosis, and treatment of cancer

“…Tumor cells can also transfer drug efflux pumps to promote drug resistance. P-Glycoprotein 80 , MDR-1 81 , and ATP-binding cassette subfamily B member 1 8 are drug efflux pumps that transmit multidrug resistance in prostate cancer, OC, leukemia, and osteosarcoma. The capacity of exosomes to transmit multidrug resistance from an adriamycin-resistant variant of MCF-7 to an adriamycin-sensitive variant of MCF-7 was achieved by controlling P-glycoprotein expression 82 .…”

Carnosine Potentiates Doxorubicin-Induced Cytotoxicity in Resistant NCI/ADR-RES Cells by Inhibiting P-Glycoprotein—In Silico and In Vitro Evidence

“…The fact that multiple factors affect the activity and expression of these transporters adds further importance to the research in this field. Modulators of P-gp activity and expression include nutritional factors such as salt intake [ 9 , 11 ], patient factors and genetic makeup [ 2 , 31 ], and the activation of various signaling pathways in cancer compared with normal cells [ 5 , 10 , 32 ]. Thus, with the help of current knowledge on the detailed domain structure of P-gp [ 15 , 17 ] and advanced in silico screening technologies [ 6 , 29 ], the search for better P-gp inhibitors shall continue to increase anticancer therapeutic efficacy and decrease patient suffering.…”

A review on terpenes for treatment of gastric cancer: current status and nanotechnology-enabled future

“…Elemene decreases the mRNA-expression level of Bcl-2 and increases the expression of the p-ERK1/2 protein along with BAX-mRNA. 80,81 2.5.3 Parthenolide. It is a sesquiterpene lactone and is a medicinal compound obtained from Parthenium, which was initially used to treat migraines, epidermal infections, and rheumatism.…”

“…Elemene decreases the mRNA-expression level of Bcl-2 and increases the expression of the p -ERK1/2 protein along with BAX-mRNA. 80,81…”