Combating P-glycoprotein-mediated multidrug resistance with 10- O -phenyl dihydroartemisinin ethers in MCF-7 cells

Zhong, Hang; Zhao, Xuan; Zuo, Zhizhong; Sun, Jing; Yao, Yao; Wang, Tao; Liú, Dan; Zhao, Liang

doi:10.1016/j.ejmech.2015.10.040

Cited by 24 publications

(9 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mechanisms underlying artemisinin-mediated anti-proliferative and apoptosis inducing role in breast cancer have also been explored [ 54 – 63 ]. Role of artemisinin in drug resistance has been studied as well [ 64 , 65 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome analysis of genes associated with breast cancer cell motility in response to Artemisinin treatment

et al. 2017

View full text Add to dashboard Cite

BackgroundWell-known anti-malarial drug artemisinin exhibits potent anti-cancerous activities. In-vivo and in-vitro studies showed its anti-tumor and immunomodulatory properties signifying it as a potent drug candidate for study. The studies of mechanisms of cell movement are relevant which can be understood by knowing the involvement of genes in an effect of a drug. Although cytotoxicity and anti-proliferative activity of artemisinin is evident, the genes participating in its anti-migratory and reduced invasive effect are not well studied. The present study reports the alteration in the expression of 84 genes involved in cell motility upon artemisinin treatment in MCF-7 breast cancer cells using pathway focused gene expression PCR array. In addition, the effect of artemisinin on epigenetic modifier HDACs is studied.MethodsWe checked the functional stimulus of artemisinin on cell viability, migration, invasion and apoptosis in breast cancerous cell lines. Using qRT-PCR and western blot, we validated the altered expression of relevant genes associated with proliferation, migration, invasion, apoptosis and mammary gland development.ResultsArtemisinin inhibited cell proliferation of estrogen receptor negative breast cancer cells with fewer efficacies in comparison to estrogen receptor positive ones. At the same time, cell viability and proliferation of normal breast epithelial MCF10A cells was un-affected. Artemisinin strongly inhibited cancer cell migration and invasion. Along with orphan nuclear receptors (ERRα, ERRβ and ERRγ), artemisinin altered the ERα/ERβ/PR/Her expression status of MCF-7 cells. The expression of genes involved in the signaling pathways associated with proliferation, migration, invasion and apoptosis was significantly altered which cooperatively resulted into reduced growth promoting activities of breast cancer cells. Interestingly, artemisinin exhibited inhibitory effect on histone deacetylases (HDACs).ConclusionsUpregulated expression of tumor suppressor genes along with reduced expression of oncogenes significantly associated with growth stimulating signaling pathways in response to artemisinin treatment suggests its efficacy as an effective drug in breast cancer treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Transcriptome analysis of genes associated with breast cancer cell motility in response to Artemisinin treatment

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, although piperazine or its derivatives did not demonstrate a powerful effect on P-gp modulation, it is still considered a potential approach because piperazine is the basic core structure of a number of pharmaceuticals for many diseases [15,16]. Moreover, in vitro investigations have shown the possibility of piperazine or derivative use for modulating MDR mediated by P-gp [17,18] and other ABC transporters, such as breast cancer resistance protein (BCRP) [25] and multidrug resistance-associated protein 1 (MRP1) [26].…”

Section: Discussionmentioning

confidence: 99%

“…Some novel compounds with 10-beta-phenyl ethers of dihydroartemisinin (DHA) with piperazine substitutions have demonstrated significant effects on transporter-mediated antiproliferation in human breast cancer cells. Among them, two DHA compounds with piperazine substitution had a 1.5–2-fold greater effect on antiproliferative activity than the DHA compounds without piperazine substitution [18]. These reports have suggested the possibility of piperazine or its analogues as potential P-gp modulators.…”

Section: Introductionmentioning

confidence: 99%

Effects of Piperazine Derivative on Paclitaxel Pharmacokinetics

Lee

Chae

et al. 2019

Pharmaceutics

View full text Add to dashboard Cite

Paclitaxel (PTX) is an anticancer agent that is used to treat many cancers but it has a very low oral bioavailability due, at least in part, to the drug efflux transporter, P-glycoprotein (P-gp). Therefore, this study was performed to enhance oral bioavailability of PTX. In this study, we investigated the effects of several piperazine derivatives on P-gp function in vitro. Compound 4 was selected as the most potent P-gp inhibitor from the in vitro results for examining the pharmacokinetic (PK) changes of PTX in rats. Compound 4 increased the AUCinf of PTX without alterations in the Cmax value. The elimination half-life was extended and the oral clearance decreased. Additionally, the Tmax was delayed or widened in the treatment groups. Therefore, the bioavailability (BA) of PTX was improved 2.1-fold following the co-administration of 5 mg/kg of the derivative. A piperazine derivative, compound 4, which was confirmed as a substantial P-gp inhibitor in vitro increased the BA of PTX up to 2-fold by a lingering absorption, in part due to inhibition of intestinal P-gp and a low oral clearance of PTX. These results suggest that co-administering compound 4 may change the PK profile of PTX by inhibiting P-gp activity in the body.

show abstract

“…According to previous reports, ART and its derivatives were sensitive to drug-resistant tumor cells, so we tried to use MNP-DHA to carry out cytotoxicity experiments on MCF-7/ADR cell lines (Zhong et al, 2016;Hu et al, 2019). As shown in Figure 2D, only 33% cell viability was obtained after treatment by MNP-DHA at a concentration of 100 µg/mL.…”

Section: In Vitro Biocompatibility and Cytotoxicity Assaysmentioning

confidence: 99%

“…et al, 2019;Yao et al, 2018;Sun et al, 2019). What's more, it has been found that ART and its derivatives showed sensitivity against multidrug resistance (MDR) cancer cells, as that some common ART-based drugs were not transported by P-glycoprotein (P-gp), which mediates cellular MDR by actively pumping antitumor drugs outside the cancer cells (Kruh and Belinsky, 2003;Szakacs et al, 2006;Prasad et al, 2012;Zhong et al, 2016;. Therefore, ART and its derivatives exhibit the potential to overcome tumor MDR.…”

Section: Introductionmentioning

confidence: 99%

Dihydroartemisinin-Loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy

et al. 2020

View full text Add to dashboard Cite

Recently, chemodynamic therapy (CDT) has represented a new approach for cancer treatment with low toxicity and side effects. Nonetheless, it has been a challenge to improve the therapeutic effect through increasing the amount of reactive oxygen species (ROS). Herein, we increased the amount of ROS agents in the Fenton-like reaction by loading dihydroartemisinin (DHA) which was an artemisinin (ART) derivative containing peroxide groups, into magnetic nanoparticles (MNP), thereby improving the therapeutic effect of CDT. Blank MNP were almost non-cytotoxic, whereas three MNP loading ART-based drugs, MNP-ART, MNP-DHA, and MNP-artesunate (MNP-AS), all showed significant killing effect on breast cancer cells (MCF-7 cells), in which MNP-DHA were the most potent. What's more, the MNP-DHA showed high toxicity to drug-resistant breast cancer cells (MCF-7/ADR cells), demonstrating its ability to overcome multidrug resistance (MDR). The study revealed that MNP could produce ferrous ions under the acidic condition of tumor microenvironment, which catalyzed DHA to produce large amounts of ROS, leading to cell death. Further experiments also showed that the MNP-DHA had significant inhibitory effect on another two aggressive breast cancer cell lines (MDA-MB-231 and MDA-MB-453 cells), which indicated that the great potential of MNP-DHA for the treatment of intractable breast cancers.

show abstract

Combating P-glycoprotein-mediated multidrug resistance with 10- O -phenyl dihydroartemisinin ethers in MCF-7 cells

Cited by 24 publications

References 24 publications

Transcriptome analysis of genes associated with breast cancer cell motility in response to Artemisinin treatment

Transcriptome analysis of genes associated with breast cancer cell motility in response to Artemisinin treatment

Effects of Piperazine Derivative on Paclitaxel Pharmacokinetics

Dihydroartemisinin-Loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy

Contact Info

Product

Resources

About