Conjugation of triphenylantimony(V) with carvacrol against human breast cancer cells

• Published in: Journal of biological inorganic chemistry 2022-04, Vol.27 (3), p.373-389
• Main Authors: Kapetana, Marianthi, Banti, Christina N., Papachristodoulou, Christina, Psycharis, Vassilios, Raptopoulou, Catherine P., Hadjikakou, Sotiris K.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Antimony; Apoptosis; Biochemistry; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Calf thymus; Carvacrol; Cell cycle; Cell death; Cymenes; Cytology; Deoxyribonucleic acid; Differential scanning calorimetry; DNA; DNA fragmentation; Ethidium bromide; Female; Fetuses; Fluorescence spectroscopy; Fourier analysis; Glutathione; Hormones; Humans; Hydrogen peroxide; Inorganic chemistry; Life Sciences; MCF-7 Cells; Metal ions; Microbiology; Mitochondria; Original Paper; Oxidation; Spectrum analysis; Tumor cell lines; Tumor cells; X-ray diffraction
• ISSN: 1432-1327; 0949-8257; 1432-1327
• DOI: 10.1007/s00775-022-01936-5

The organoantimony derivative of formula trans -O,O-[Ph 3 Sb V (Carv) 2 ] ( TPAC ) (CarvH = carvacrol) is obtained by the oxidation of triphenylstibine (Ph 3 Sb III ) with hydrogen peroxide in the presence of carvacrol (CarvH). Physical methods such as X-ray Fluorescence (XRF) spectroscopy, single crystal and powder X-ray diffraction analysis (XRD and PXRD), Attenuated Total Reflection Fourier Transform Infra-red (ATR-FTIR) spectroscopy, Thermogravimetric Differential Thermal Analysis (TG–DTA) and Differential Scanning Calorimetry (DTG/DSC), confirm the retention of the formula of TPAC throughout the sample mass in solid state, while UV–Vis spectroscopy in the solution. TPAC is the first example of carvacrol (the main ingredient of oregano) covalently bonded to any metal ion. Only the trans -O,O-[Ph 3 Sb(Carv) 2 ] isomer was isolated suggesting stereo-selectivity of the preparation route. TPAC inhibits in vitro both human breast adenocarcinoma cell lines: MCF-7 (positive to hormones receptor (HR +)), MDA-MB-231 (negative to hormones receptor (HR-)) stronger than normal human fetal lung fibroblast cells (MRC-5). The MCF-7 cells morphology, DNA fragmentation, Acridine Orange/Ethidium Bromide (AO/EB) Staining, cell cycle arrest and mitochondrial membrane permeabilization tests suggest an apoptotic pathway for cell death, especially, through the mitochondrion damage. The binding type of TPAC toward the calf thymus CT-DNA was initially deduced ex vivo from the differentiation of the DNA solution viscosity. Fluorescence spectroscopy confirms the interaction mode suggested. Spectroscopic evidence (FTIR, UV–Vis) suggest that glutathione (GSH) (a tripeptide over-expressed in tumor cells) induces conversion of non-active pentavalent antimony, which is contained in TPAC, to active trivalent one, providing a new strategy for the development of targeted chemotherapeutics. Graphical abstract