Prodigiosin/PU-H71 as a novel potential combined therapy for triple negative breast cancer (TNBC): preclinical insights

• Published in: Scientific reports 2020-09, Vol.10 (1), p.14706-14706, Article 14706
• Main Authors: Anwar, Mohammed Moustapha, Shalaby, Manal, Embaby, Amira M., Saeed, Hesham, Agwa, Mona M., Hussein, Ahmed
• Format: Article
• Language: English
• Subjects: 631/61; 631/67; Annealing; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Benzodioxoles - pharmacology; Breast cancer; Caspases - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Copper; Cytotoxicity; Drug Evaluation, Preclinical; Drug resistance; Electrochemistry; ErbB Receptors - metabolism; Female; High temperature; HSP90 Heat-Shock Proteins - metabolism; Humanities and Social Sciences; Humans; Metabolites; multidisciplinary; Nanotechnology; Oxidation; Oxides; Prodigiosin - pharmacology; Purines - pharmacology; Science; Science (multidisciplinary); Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Triple Negative Breast Neoplasms - drug therapy; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-71157-w

Prodigiosin, a secondary metabolite red pigment produced by Serratia marcescens , has an interesting apoptotic efficacy against cancer cell lines with low or no toxicity on normal cells. HSP90α is known as a crucial and multimodal target in the treatment of TNBC. Our research attempts to assess the therapeutic potential of prodigiosin/PU-H71 combination on MDA-MB-231 cell line. The transcription and protein expression levels of different signalling pathways were assessed. Treatment of TNBC cells with both drugs resulted in a decrease of the number of adherent cells with apoptotic effects. Prodigiosin/PU-H71 combination increased the levels of caspases 3,8 and 9 and decreased the levels of mTOR expression. Additionally, there was a remarkable decrease of HSP90α transcription and expression levels upon treatment with combined therapy. Also, EGFR and VEGF expression levels decreased. This is the first study to show that prodigiosin/PU-H71 combination had potent cytotoxicity on MDA-MB-231 cells; proving to play a paramount role in interfering with key signalling pathways in TNBC. Interestingly, prodigiosin might be a potential anticancer agent to increase the sensitivity of TNBC cells to apoptosis. This study provides a new basis for upcoming studies to overcome drug resistance in TNBC cells.