Abstract
Drug repurposing is currently an important approach for accelerating drug discovery and development for clinical use. Hepatocellular carcinoma (HCC) presents drug resistance to chemotherapy, and the prognosis is poor due to the existence of liver cancer stem-like cells. In this study, we investigated the effect of the neuroleptic agent pimozide to inhibit stem-like cell maintenance and tumorigenicity in HCC. Our results showed that pimozide functioned as an anti-cancer drug in HCC cells or stem-like cells. Pimozide inhibited cell proliferation and sphere formation capacities in HCC cells by inducing G0/G1 phase cell cycle arrest, as well as inhibited HCC cell migration. Surprisingly, pimozide inhibited the maintenance and tumorigenicity of HCC stem-like cells, particularly the side population (SP) or CD133-positive cells, as evaluated by colony formation, sphere formation and transwell migration assays. Furthermore, pimozide was found to suppress STAT3 activity in HCC cells by attenuating STAT3-dependent luciferase activity and down-regulating the transcription levels of downstream genes of STAT3 signaling. Moreover, pimozide reversed the stem-like cell tumorigenic phenotypes induced by IL-6 treatment in HCC cells. Further, the antitumor effect of pimozide was also proved in the nude mice HCC xenograft model. In short, the anti-psychotic agent pimozide may act as a novel potential anti-tumor agent in treating advanced HCC.
Highlights
New advances in drug discovery and development, to make pharmaceutical research more predictable and reliable are urgently needed [1]
We examined the effect of pimozide on Hepatocellular carcinoma (HCC) cells using CFSE staining
The data showed that the specific regions of CFSE staining in MHCC-97L and Hep 3B cells treated with pimozide for 48 h were greater than that of the control (p < 0.01) (Figure 1B)
Summary
New advances in drug discovery and development, to make pharmaceutical research more predictable and reliable are urgently needed [1]. One of the most important approaches is drug repurposing, in which new applications for existing or abandoned pharmacotherapies are investigated [2, 3]. In cancer therapy, this technique has achieved affordable results, with new uses found for existing drugs [4]. The use of imatinib (Gleevec), a drug that was originally developed to treat chronic myelogenous leukaemia, has been expanded to treat several malignancies due to its targeting of similar signaling pathways [8], such as those in gastrointestinal stromal tumors [9] and colorectal cancers [10]. Finding new uses for existing drugs represents an effective strategy for developing novel pharmacotherapies to treat cancer cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
