Abstract
ABCB1 is one of the major drug efflux transporters that is known to cause multidrug resistance (MDR) in cancer patients receiving chemotherapy for the treatment of solid tumors and hematological malignancies. Inhibition of ABCB1 efflux function is important for maintaining the intracellular concentration of chemotherapeutic drugs. Here, we evaluated ciprofloxacin for its ability to reverse MDR caused by the overexpression of ABCB1. Cytotoxicity of ciprofloxacin was determined by the MTT assay. The chemosensitizing effects of ciprofloxacin were determined in combination with ABCB1 substrates. The intracellular accumulation and efflux of ABCB1 substrates was measured by a scintillation counter, and protein expression was determined by the Western blotting. Vanadate-sensitive ATPase assay was performed to determine the effect of ciprofloxacin on the ATPase activity of ABCB1, and docking analysis was done to determine the interaction of ciprofloxacin with ABCB1. Ciprofloxacin significantly potentiated the cytotoxic effects of ABCB1 substrates in ABCB1-overexpressing cells. Furthermore, ciprofloxacin increased the intracellular accumulation and decreased the efflux of [3H]-paclitaxel without altering the expression of ABCB1. Ciprofloxacin stimulated the ATPase activity of ABCB1 in a concentration-dependent manner. Our findings showed that ciprofloxacin potently inhibits the ABCB1 efflux function and it has potential to be developed as a combination anticancer therapy.
Highlights
Chemotherapy remains the most successful and reliable treatment option for combating hematological malignancies and solid tumors [1,2,3]
Studies have shown that ciprofloxacin inhibits the cellular proliferation of melanoma cells B16F10, triple-negative breast cancer cells MDA-MB−231, pancreatic cancer cells Panc−1, non-small cell lung cancer cells A549, and hepatocellular carcinoma cells HepG2 [28,29,30,31]
One major finding of this study was that ciprofloxacin (1, 5, and 10 μM. Verapamil (10 μM)), in a concentrationdependent manner, significantly sensitized the ABCB1-overexpressing cells to the substrates of ABCB1
Summary
Chemotherapy remains the most successful and reliable treatment option for combating hematological malignancies and solid tumors [1,2,3]. The chronic use of chemotherapeutic drugs renders cancer cells insensitive, requiring a higher dose of the drug to exert the same pharmacological effect. This phenomenon of the development of insensitivity in cancer cells to a wide variety of chemotherapeutic drugs that have different structures and mechanisms of action is referred to as multidrug resistance (MDR) [4,5,6]. The development of MDR in cancer cells is known to be the major factor hindering the success of chemotherapy in clinics [7,8,9]. The ATP-binding cassette (ABC) transporters-mediated efflux of chemotherapeutic drugs remains the most prominent mechanism causing MDR [10,11].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
