Effect of low dose metronomic therapy on MCF-7 tumor cells growth and angiogenesis. Role of muscarinic acetylcholine receptors

SANCHEZ F; SALES ME; SANCHEZ F; SALES ME; SALEM A; SANCHEZ Y; SALEM A; SANCHEZ Y; MARTINEZ PULIDO P; ESPAÑOL A; MARTINEZ PULIDO P; ESPAÑOL A

INTERNATIONAL IMMUNOPHARMACOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2020

1567-5769

The non-neuronal cholinergic system refers to the presence of acetylcholine, choline acetyltransferase, acetylcholinesteraseand cholinergic receptors, nicotinic and muscarinic (mAChRs) expressed in non-neuronal cells.The presence of mAChRs has been detected in different type of tumor cells and they are linked with tumorigenesis.We had previously documented the expression of mAChRs in murine and human mammary adenocarcinomasand the absence of these receptors in normal mammary cells of the same origins. We also demonstratedthat mAChRs are involved in breast cancer progression, pointing to a main role for mAChRs as oncogenicproteins. Since the long term treatment of breast cancer cells with the muscarinic agonist carbachol promotedcell death, here we investigated the ability of low doses of this agonist combined with paclitaxel (PX), a taxaneusually administered to treat breast cancer, to inhibit the progression of human MCF-7 tumor cells. We demonstratedthat PX plus carbachol reduced cell viability and tumor growth in vitro probably due to a downregulationin cancer stem cells population and in the expression of ATP ?binding cassette? G2 drug extrusionpump; also a reduction in malignant-induced angiogenesis was produced by the in vivo administration of thementioned combination in a metronomic schedule to MCF-7 tumor-bearing NUDE mice. Our results confirm thatmAChRs could be considered as therapeutic targets for metronomic therapy in breast cancer as well as theusefulness of a muscarinic agonist as repositioning drug in the treatment of this type of tumors.