title: Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types.
abstract: Breast cancer (BC) is the most common cause of cancer-related death worldwide. Although platinum-based drugs (PBDs) are effective anticancer agents, responsive patients eventually become resistant. While resistance of some cancers to PBDs has been explored, the cellular responses of BC cells are not studied yet. Therefore, we aim to assess the differential effects of PBDs on BC ultrastructure. Three representative cells were treated with different concentrations and timing of Cisplatin, Carboplatin, and Oxaliplatin. Changes on cell surface and ultrastructure were detected by scanning (SEM) and transmission electron microscope (TEM). In SEM, control cells were semiflattened containing microvilli with extending lamellipodia while treated ones were round with irregular surface and several pores, indicating drug entry. Prolonged treatment resembled distinct apoptotic features such as shrinkage, membrane blebs, and narrowing of lamellipodia with blunt microvilli. TEM detected PBDs' deposits that scattered among cellular organelles inducing structural distortion, lumen swelling, chromatin condensation, and nuclear fragmentation. Deposits were attracted to fat droplets, explained by drug hydrophobic properties, while later they were located close to cell membrane, suggesting drug efflux. Phagosomes with destructed organelles and deposits were detected as defending mechanism. Understanding BC cells response to PBDs might provide new insight for an effective treatment.
authors.affiliation: Department of Allied Health Sciences, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Shadia
authors.identifier: 0000-0001-6150-4024
authors.initials: S
authors.lastname: Al-Bahlani
authors.affiliation: Department of Allied Health Sciences, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Buthaina
authors.identifier: 0000-0003-2821-6615
authors.initials: B
authors.lastname: Al-Dhahli
authors.affiliation: Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Kawther
authors.initials: K
authors.lastname: Al-Adawi
authors.affiliation: Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Abdurahman
authors.initials: A
authors.lastname: Al-Nabhani
authors.affiliation: Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Al-Kindi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000648:ultrastructure; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010588:Phagosomes / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016190:Carboplatin; D002945:Cisplatin