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Review
. 2019 Aug 28;11(9):1258.
doi: 10.3390/cancers11091258.

Neurokinin-1 Receptor Antagonists against Hepatoblastoma

Miguel Muñoz  1 , Marisa Rosso  2 , Rafael Coveñas  3
Affiliations
Review

Neurokinin-1 Receptor Antagonists against Hepatoblastoma

Miguel Muñoz et al. Cancers (Basel). .

Abstract

Hepatoblastoma (HB) is the most common malignant liver tumor that occurs during childhood. The prognosis of children with HB is favorable when a complete surgical resection of the tumor is possible, but for high-risk patients, the prognosis is much worse. New anti-HB strategies must be urgently developed. The undecapeptide substance P (SP) after binding to the neurokinin-1 receptor (NK-1R), regulates cancer cell proliferation, exerts an antiapoptotic effect, induces cell migration for invasion/metastasis, and triggers endothelial cell proliferation for neoangiogenesis. HB samples and cell lines overexpress NK-1R (the truncated form) and SP elicits HB cell proliferation. One of these strategies could be the use of non-peptide NK-1R antagonists. These antagonists exert, in a concentration-dependent manner, an antiproliferative action against HB cells (inhibit cell proliferation and induce the death of HB cells by apoptosis). NK-1R antagonists exerted a dual effect in HB: Decreased both tumor volume and angiogenic activity. Thus, the SP/NK-1R system is an important target in the HB treatment and NK-1R antagonists could act as specific drugs against HB cells. In this review, we update and discuss the use of NK-1R antagonists in the treatment of HB.

Keywords: NK-1 receptor; angiogenesis; antitumor; apoptosis; aprepitant; hepatoblastoma; substance P.

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Conflict of interest statement

USPTO Application no. 20090012086 “Use of non-peptidic NK-1 receptor antagonists for the production of apoptosis in tumor cells” (Miguel Muñoz). No conflict of interest (Marisa Rosso and Rafael Coveñas).

Figures

Figure 1
Figure 1
The substance P/neurokinin-1 receptor (SP/NK-1R) system regulates several cell signaling pathways involved in cancer progression. These pathways are the following: (a) Antiapoptotic signaling pathway (PI3K/Akt/mTOR); (b) cell proliferation signaling pathway (PKC, MAPKs, ERK); (c) cell migration signaling pathway (Rho-ROCK-pMLC); (d) Wnt signaling pathway (β-catenin, c-myc, cyclin D1); (e) AC-cAMP-PKA phosphorylation signaling pathway, and (f) the Warburg effect (GSK-3β). APC: Adenomatous polyposis coli; Dvl: Dishevelled; Fzd: Frizzled receptor; PCP: Planar cell polarity pathway; PDK-1: Phosphoinositide-dependent kinase-1; pMLC: Myosin light-chain kinase; TCF/LEF: Transcription factor/lymphoid enhancer-binding factor.
See this image and copyright information in PMC

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