The neurokinin-1 receptor antagonist aprepitant is a promising candidate for the treatment of breast cancer

Abstract

The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in the development of cancer. No in-depth studies of the involvement of this system in breast cancer (BC) have been carried out, and the action exerted by the drug aprepitant on BC cells is currently unknown. We show the involvement of this system in human BC cell lines: i) these cells express mRNA for the NK-1 receptor; ii) they overexpress NK-1 receptors; iii) the NK-1 receptor is involved in their viability; iv) SP induces their proliferation; v) NK-1 receptor antagonists block SP-induced mitogen stimulation of these cells; vi) the specific antitumor action of such antagonists on these cells occurs through the NK-1 receptor; and vii) BC cell death is due to apoptosis. We also found NK-1 receptors and SP in all human BC samples studied. The NK-1 receptor may be a promising target in the treatment of BC and NK-1 receptor antagonists could be candidates as a new antitumor drug in the treatment of BC.

Targeting tachykinin receptors in neuroblastoma

“…This is in line with previous reports by Munoz M. et al describing anti-tumoral activity of fosaprepitant in various adult tumor cell lines [10, 13, 14]. Similar to previous reports, we observed that inhibiting TACR1 with fosaprepitant did not affect all cell lines to the same degree.…”

“…TACR1 is linked to a variety of physiological and biological processes that include the regulation of neurotransmission, pain, inflammation, cell growth and differentiation [8, 9]. Some recent studies have proposed tachykinin receptor involvement in oncogenesis [10–14]. TACR1 activation by substance P initiates phosphoinositide hydrolysis to mobilize intracellular calcium and active calcium-dependent signaling via kinases, such as the SRC kinase [15, 16].…”

“…Pharmaceutically blocking tachykinin receptor signaling in colon cancer, breast cancer, hepatoblastoma, osteosarcoma, acute lymphoblastic leukemia and neuroblastoma cancer cell lines was found to inhibit cell growth, and treatment of mice with osteosarcoma xenografts resulted in reduced tumor burden. This previous evidence makes tachykinin receptors a putative target for future anticancer strategies [10, 12, 14]. …”

SP/NK‐1R promotes gallbladder cancer cell proliferation and migration

“…Over the past decades, the function of peptides and their receptors in tumors have attracted growing interest, and research efforts show that these peptides and receptors can influence cancer progress. One such target could be SP/NK‐1R system, since it is known that NK‐1R can act as a mitogen on several human cancers . Currently, it is still unknown whether NK‐1R exists the same effect in GBC.…”

Aprepitantın İnsan Glioblastoma U87MG Hücreleri üzerinde Antiproliferatif ve Apoptotik Etkileri

“…Ayrıca beyin tümörü in vivo modelinde de, 3 mg/kg/gün dozundaki aprepitantın beyin tümörü çevresindeki ödemi iyileştirdiği açıklanmıştır (31). Meme kanser hücreleri ile yapılan başka bir çalışmada da aprepitantın farklı meme kanser hücreleri olan BT-474, MCF-7 and MDA-MB-468 ve MT-3 üzerinde IC 50 konsantrasyonunun 10-60 μM arasında değiştiği ve kanser hücreleri üzerinde önemli sitotoksik etki yaptığı açıklanmıştır (32).…”