Breast cancer: Muscarinic receptors as new targets for tumor therapy

Abstract

The development of breast cancer is a complex process that involves the participation of different factors. Several authors have demonstrated the overexpression of muscarinic acetylcholine receptors (mAChRs) in different tumor tissues and their role in the modulation of tumor biology, positioning them as therapeutic targets in cancer. The conventional treatment for breast cancer involves surgery, radiotherapy, and/or chemotherapy. The latter presents disadvantages such as limited specificity, the appearance of resistance to treatment and other side effects. To prevent these side effects, several schedules of drug administration, like metronomic therapy, have been developed. Metronomic therapy is a type of chemotherapy in which one or more drugs are administered at low concentrations repetitively. Recently, two chemotherapeutic agents usually used to treat breast cancer have been considered able to activate mAChRs. The combination of low concentrations of these chemotherapeutic agents with muscarinic agonists could be a useful option to be applied in breast cancer treatment, since this combination not only reduces tumor cell survival without affecting normal cells, but also decreases pathological neo-angiogenesis, the expression of drug extrusion proteins and the cancer stem cell fraction. In this review, we focus on the previous evidences that have positioned mAChRs as relevant therapeutic targets in breast cancer and analyze the effects of administering muscarinic agonists in combination with conventional chemotherapeutic agents in a metronomic schedule.

The Expression of Trace Amine-Associated Receptors (TAARs) in Breast Cancer Is Coincident with the Expression of Neuroactive Ligand–Receptor Systems and Depends on Tumor Intrinsic Subtype

“…All histamine receptors are expressed in BC and are suggested to be involved in tumor growth regulation [ 88 , 89 ]. Other rhodopsin-like receptors were also co-expressed with several TAARs, including muscarinic receptors, whose stimulation leads to BC cell growth [ 84 , 90 ]. These receptors are expressed in malignant breast tumors but not in normal breast tissue [ 84 ].…”

Bioinformatic identification of hub genes related to Obesity paradox in Breast Cancer by Menopausal Status

“…Five different mAChR have been identi ed in mammals (M1-M5). In breast cancer major expression of M2/M3 subtypes was con rmed [20].…”

Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells

“…Then, strips were incubated with anti-rabbit immunoglobulin G coupled to horseradish peroxidase diluted 1:10,000 in 20 mmol/L Tris-HCl buffer, 150 mmol/L NaCl and 0.05% Tween 20 at 37℃ for 1 h. Bands were visualized by chemiluminescence. The results of densitometric analysis are expressed as optical density units relative to the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH; Santa Cruz Biotechnology Inc., San Diego, CA, USA), which was used as loading control [ 36 ].…”

“…Then, lysates were left in an ice bath for 60 min and later centrifuged at 750 g for 10 min at 4℃. Supernatants were saved at −80℃ and protein concentration was analyzed by the Bradford assay [35]. Samples (70 μg protein per lane) were subjected to 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis minigel electrophoresis, transferred to nitrocellulose membranes, and incubated overnight with rabbit anti-human ABCG2 polyclonal antibodies (Santa Cruz Biotechnology Inc., Dallas, Texas, USA) diluted 1:200.…”