Abstract
Identification of novel proteins with changed expression in resistant cancer cells could be helpful in elucidation mechanisms involved in the development of acquired resistance to paclitaxel. In this study, we carried out a 2D-PAGE using the mitochondrial-enriched fraction from paclitaxel-resistant MCF7/PacR cells compared to original paclitaxel-sensitive MCF7 breast cancer cells. Differentially expressed proteins were identified employing mass spectrometry. We found that lysosomal cathepsin D and mitochondrial abhydrolase-domain containing protein 11 (ABHD11) had decreased expression in MCF7/PacR cells. On the other hand, mitochondrial carbamoyl-phosphate synthetase 1 (CPS1) and ATPase family AAA-domain containing protein 3A and 3B (ATAD3A, ATAD3B) were overexpressed in MCF7/PacR cells. Further, we showed that there was no difference in localization of CPS1 in MCF7 and MCF7/PacR cells. We demonstrated a significant increase in the number of CPS1 positive MCF7/PacR cells, using FACS analysis, compared to the number of CPS1 positive MCF7 cells. Silencing of CPS1 expression by specific siRNA had no significant effect on the resistance of MCF7/PacR cells to paclitaxel. To summarize, we identified several novel proteins of a mitochondrial fraction whose role in acquired resistance to paclitaxel in breast cancer cells should be further assessed.
Highlights
Breast cancer is the most commonly diagnosed cancer in women with 1.67 × 106 newly diagnosed cases and nearly 5 × 105 deaths per year [1]
We detected three mitochondrial proteins (CPS1, ATAD3A/ATAD3B, and abhydrolase-domain containing protein 11 (ABHD11)) and one lysosomal protein with different expressions in paclitaxel-resistant MCF7/PacR breast cancer cells compared to paclitaxel-sensitive MCF7 breast cancer cells
None of these mitochondrial proteins have previously been associated with acquired resistance of breast cancer cells to paclitaxel
Summary
Breast cancer is the most commonly diagnosed cancer in women with 1.67 × 106 newly diagnosed cases and nearly 5 × 105 deaths per year [1]. Because of the heterogeneous nature of breast cancer, chemotherapy is based on various anticancer agents [2]. Specific chemotherapy by aromatase inhibitors (i.e., Tamoxifen ®) for estrogen-positive breast cancer or monoclonal antibody (i.e., Trastuzumab ®) for HER2 positive breast cancer can be useful when used in combination with anthracyclines (Doxorubicin, Epirubicin) and taxanes (Paclitaxel, Taxol®, and Docetaxel, Taxotere®) [3,4]. Taxanes and anthracyclines are the preferred choices for the treatment of triple-negative breast cancer [4,5]. The anticancer effect of paclitaxel (Taxol ®) was discovered while testing yew (Taxus brevifolia) bark extract on cancer cell proliferation [6]. The cells arrested in mitosis may exit mitosis and die via various mechanisms, survive as senescent cells, or may be able to duplicate as aneuploid cells [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
