• To overcome drug resistance in MDA-MB-231 breast cancer cells via paclitaxel loaded nanoemulsion
  • Farnoosh Attari,1,* Habibullah Hazim,2 Hasan Rafati,3
    1. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
    2. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
    3. Department of Phytochemistry & Chemical Engineering, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran


  • Introduction: Paclitaxel (PTX), is considered as one of the most effective chemotherapeutic compounds in treatment of several tumors including breast cancer. Nevertheless, one of the main problems regarding this reagent in clinical trials is the developed drug resistance over the time. There are some mechanisms proposed for the PTX resistance including alteration of microtubule regulatory proteins and deregulation of apoptotic signaling pathway. Since high percentage of PTX resistance in patients would be detectable at the time of initial diagnosis, it seems necessary to search for a new tactic to bypass the PTX resistance. One of the most efficient strategies to circumvent drug resistance would be nano-based drug delivery systems among which nanoemulsions are the ones with less toxicity. The size of the nanoemulsions varies from 20 nm to 200 nm which makes them suitable vehicles to increase the solubility and oral bioavailability of hydrophobic drugs such as PTX. Nevertheless, so far, few studies reported the nanoemulsions application for bypassing drug resistance. In the current study, to overcome PTX resistance in breast cancer cells, we have established a new nanoemulsion system containing PTX (PTX- NE).
  • Methods: High speed homogenization method was employed to fabricate the Satureja khuzestanica essential oil nanoemulsion and afterwards, PTX was loaded into it to achieve PTX-nanoemulsion (PTX-NE). To make sure of the size of the fabricated PTX-NE, the DLS technique was used. Next, MTT assay was performed to evaluate the cytotoxicity effects of free PTX compared to PTX-NE on drug resistant MDA-MB-231 cells.
  • Results: We have employed different concentrations of PTX (10nm, 50nm, 100nm, 200nm, 500nm, 1µm & 10µm) on MDA-MB-231 breast cancer line for 24, 48 and 72 hours to assess their viability. Our results indicated that we could not achieve IC50 concentration in these cells even after 72 hours treatment with the mentioned concentrations of PTX, which was indicative of drug resistance. To overcome this resistance, we have used noneffective dose of TPGS, a derivative of vitamin E and an inhibitor of MDR pump, combined with PTX in order to achieve IC50 concentration for PTX. The data illustrated that combined with TPGS, 500nm concentration of PTX could kill almost 59% of the resistant cells. For the next step we wondered what would be the effect of PTX-NE without TPGS on the cell viability. Interestingly, The IC50 value of PTX from PTX-NE in resistant MDA-MB-231 cells was greatly reduced to 250nm, which was even less than the IC50 in TPGS-PTX combination treatment.
  • Conclusion: The nanoemulsion of Satureja khuzestanica essential oil performed as a stable drug delivery system for paclitaxel which led to reduction of PTX concentration due to developed synergistic effect and also drug resistance reversal in MDA-MB-231 cells. Hence, the severe PTX resistance in breast cancer could be effectively reduced by PTX-NE, which could deliver a potential strategy to treat multidrug resistance in this type of cancer.
  • Keywords: Drug resistance, Breast cancer, Nanoemulsion, Paclitaxel