Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX)

Abstract

Multidrug resistance (MDR) has become a major obstacle in the treatment of cancer, and is associated with mechanisms such as increased drug outflow, reduction of apoptosis, and/or altered drug metabolism. These problems can be mitigated by the coadministration of agents known as chemosensitizers, as they can reverse resistance to anticancer drugs and eventually resensitize cancer cells. We explore the chemosensitizing effect of Achillin, a guaianolide-type sesquiterpene lactone isolated from the Mexican medicinal plant Artemisia ludovisiana, to reverse MDR in Hep3B/PTX cells of hepatocellular carcinoma, which present resistance to paclitaxel (PTX). Achillin showed an important effect as chemosensitizer; indeed, the cytotoxic effect of PTX (25 nM) was enhanced, and the induction of G2/M phase cell cycle arrest and apoptosis were potentiated when combining with Achillin (100 μM). In addition, we observed that Achillin decreases P-gp levels and increases the intracellular retention of doxorubicin in Hep3B/PTX cells; in addition, homology structural modeling and molecular docking calculations predicted that Achillin interacts in two regions (M-site and R-site) of transporter drug efflux P-glycoprotein (P-gp). Our results suggest that the chemosensitizer effect demonstrated for Achillin could be associated with P-gp modulation. This work also provides useful information for the development of new therapeutic agents from guaianolide-type sesquiterpene lactones like Achillin.

Calebin A Potentiates the Effect of 5-FU and TNF-β (Lymphotoxin α) against Human Colorectal Cancer Cells: Potential Role of NF-κB

“…Indeed, tumor cells are rapidly developing resistance to the majority of chemotherapeutic drugs resulting in tumor recurrence [67][68][69]. Interestingly, it has been shown that an abundance of natural substances may be used as adjuvants in cancer treatment regimens to reverse chemoresistance to chemotherapeutic drugs [70,71]. Several reports from ours and other laboratories have reported that tumor cells can acquire drug resistance by different mechanisms including mutation or overexpression of the drug target, inactivation of the drug or removal of the drug from the cell [16,72,73].…”

In Silico Studies of Lamiaceae Diterpenes with Bioinsecticide Potential against Aphis gossypii and Drosophila melanogaster

“…The results of the ligand efficiency (LE) [ 108 , 109 ] are also available as a parameter to evaluate the best diterpenes ( Table 4 and Table 5 ). The selected diterpenes for Aphis showed LE close to the insecticides while for Drosophila are similar or superior, suggesting this class of compounds as potential bioinsecticides.…”

Stevia Genus: Phytochemistry and Biological Activities Update

“…This guaianolide-type sesquiterpene lactone has shown anti-inflammatory, antiallergic (IC 50 = 100 µM) and cytotoxic activity on SMMC-7721 cell lines [ 67 ]. Sanchez-Carranza et al [ 68 ] demonstrated that achillin enhances the cytotoxic effect of paclitaxel and the induction of G2/M phase cell cycle arrest and apoptosis when associating both drugs. This guainolide also reduced P-gp levels and increased the intracellular retention of doxorubicin in Hep3B/PTX cells.…”