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

Marianthi Kapetana; Christina N Banti; Christina Papachristodoulou; Vassilios Psycharis; Catherine P Raptopoulou; Sotiris K Hadjikakou

doi:10.1007/s00775-022-01936-5

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

J Biol Inorg Chem. 2022 Apr;27(3):373-389. doi: 10.1007/s00775-022-01936-5. Epub 2022 Mar 17.

Authors

Marianthi Kapetana¹, Christina N Banti², Christina Papachristodoulou³, Vassilios Psycharis⁴, Catherine P Raptopoulou⁴, Sotiris K Hadjikakou^{5

6}

Affiliations

¹ Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece.
² Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece. cbanti@uoi.gr.
³ Department of Physics, University of Ioannina, 45110, Ioannina, Greece.
⁴ Institute of Nanoscience and Nanotechnology, National Center for Scientific Research "Demokritos", 15310, Athens, Greece.
⁵ Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece. shadjika@uoi.gr.
⁶ Institute of Materials Science and Computing, University Research Center of Ioannina (URCI), 45110, Ioannina, Greece. shadjika@uoi.gr.

PMID: 35301595
DOI: 10.1007/s00775-022-01936-5

Abstract

The organoantimony derivative of formula trans-O,O-[Ph₃Sb^V(Carv)₂] (TPAC) (CarvH = carvacrol) is obtained by the oxidation of triphenylstibine (Ph₃Sb^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-[Ph₃Sb(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.

Keywords: Apoptosis; Biological inorganic chemistry; Carvacrol; Cytotoxicity; Natural product; Pentavalent antimony metallodrugs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Breast Neoplasms* / drug therapy
Breast Neoplasms* / pathology
Cymenes
DNA
Female
Hormones
Humans
MCF-7 Cells

Substances

Cymenes
Hormones
DNA
carvacrol