Title:Muscarinic Receptors as Targets for Metronomic Therapy in Breast Cancer
Volume: 22
Issue: 14
Author(s): María Elena Sales
Affiliation:
Keywords:
Acetylcholine, muscarinic receptors, signal transduction pathways, tumor progression, breast cancer, metronomic therapy.
Abstract: Background: It is actually known that acetylcholine works as a signaling molecule in non-neuronal cells
and tissues, in addition to its neuronal function as neurotransmitter. It can act on two types of receptors nicotinic
and muscarinic receptors (mAChRs). The latter belong to the G protein coupled receptor family and there are five
subtypes genetically cloned. Their activation triggers classical and non-classical intracellular signals that could be
linked to the proliferation of normal and/or transformed cells. The M3 subtype was identified in different types of
tumors and its stimulation with agonists triggers cell proliferation, migration, invasion and metastasis. Results: Our
laboratory has extensively investigated the expression and function of mAChRs in breast tumors from animal and
human origins. We found a profuse expression of mAChRs in breast tumors, but opposite to this, an absence of
these receptors in normal breast cells and tissues. The stimulation of mAChRs with the cholinergic agonist carbachol
for 20 h increased tumor cell death. Moreover, the combination of subthreshold concentrations of the agonist with paclitaxel potentiates
cell death. The usage of low dose chemotherapy with short drug free intervals was named metronomic therapy and it has
emerged as a novel regimen for cancer treatment with very low incidence of side effects. Conclusion: Our work and that of others indicate
that mAChRs that are over-expressed in different types of tumor cells could be a useful target for metronomic therapy in cancer
treatment.
