Evaluation of Chloroquine and Hydroxychloroquine Efficacy on Chemotherapy Treatment in triple negative Breast Cancer by continuous live Cell Imaging

Triple negative breast cancer is heterogeneous type of breast cancer which, due to its high proliferation, aggressiveness, rapid progression and poor prognosis, is still a challenge to treat. These characteristics, together with distant metastasis, make this breast cancer subtype resistant to standard treatment. With the lack of targeted therapy, conventional chemotherapy is still the only established treatment option, where mostly taxanes and anthracyclines are chemotherapy of choice. Therefore, there is a need for investigation and development of new effective therapy regimens with goal to improve clinical therapy outcomes. Recently, it has been reported that autophagy has a protective role in response to anti-tumor treatments in many cancer types, including breast cancer, leading to chemotherapy resistance and has gained significant interest in cancer research. Here, we assessed the role of autophagy inhibitors, chloroquine and hydroxychloroquine on MDAMB-231 TNBC cell line and chemotherapy drug efficacy in this cell line when these autophagy inhibitors were administrated in combination with chemotherapy, camptothecin and gemcitabine. The cell responses were observed by continuous live cell imaging, robust method that enables detection of dynamic morphological changes, thus providing better insights of complex cellular processes. Our data suggest that when MDA-MB231 cells were ptretreated with either 30 µM chloroquine or 30 µM hydroxychloroquine followed by chemotherapy drug administration, in this case gemcitabine and camptothecin, dead cell area was in significant increase, compared to drugs given as single agents. Moreover, even when chemotherapy drugs were administrated at lower doses after chloroquine and hydroxychloroquine pretreatment it followed the same pattern of significant dead cell area increase. These findings indicate potential anti-cancer effect of both chloroquine and hydroxychloroquine and suggest further clinical investigation of these autophagy inhibitors in combination with chemotherapeutics and in different cancer types due to their potential value in the development of novel cancer therapies.