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Colorectal cancer (CRC) is a type of malignant tumor that seriously threatens human health and life, and its treatment has always been a difficulty and hotspot in research. Herein, this study for the first time reports that antipsychotic aripiprazole (Ari) against the proliferation of CRC cells both in vitro and in vivo , but with less damage in normal colon cells. Mechanistically, the results showed that 5-hydroxytryptamine 2B receptor (HTR2B) and its coupling protein G protein subunit alpha q (G α q) were highly distributed in CRC cells. Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling. Blockade of HTR2B signaling suppressed the growth of CRC cells, but HTR2B was not found to have independent anticancer activity. Interestingly, the binding of G α q to HTR2B was decreased after Ari treatment. Knockdown of G α q not only restricted CRC cell growth, but also directly affected the anti-CRC efficacy of Ari. Moreover, an interaction between Ari and G α q was found in that the mutation at amino acid 190 of G α q reduced the efficacy of Ari. Thus, these results confirm that G α q coupled to HTR2B was a potential target of Ari in mediating CRC proliferation. Collectively, this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent. The antipsychotic drug aripiprazole (Ari) inhibits the proliferation of colorectal cancer cells by targeting G α q coupled HTR2B. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Aims The purpose of this study was to demonstrate how curcumol affected the expression of miR-21 and whether its effects on miR-21 was associated with the activation of PTEN/PI3K/Akt pathways in CRC cells. Main methods MTT and xenograft assay were used to examine how curcumol inhibits colorectal cancer (CRC) cells' growth. Q-PCR and western blot analysis were employed to test the role of miR-21 in the inhibition of curcumol on proliferation and PTEN/PI3K/Akt pathways of CRC cells. Key findings We found that curcumol effectively inhibited CRC cells from proliferating via the PTEN/PI3K/Akt pathways and reduced expression of miR-21 both in vitro and in vivo. miR-21 mimics were found to decrease the protein level of PTEN and increase the expression of PI3K, phospho-Akt (p-Akt) and NF-κB, while miR-21 sponge (miR-21-SP) enhanced the expression of PTEN and reduced the activity of PI3K, Akt and NF-κB. Furthermore, miR-21-SP strengthened the role of curcumol in up-regulating PTEN and inhibiting PI3K/Akt pathways, but miR-21 reversed the effect of curcumol on the PTEN/PI3K/Akt pathways. Significance Our research demonstrated that curcumol reduced the proliferation of CRC cells through PTEN/PI3K/Akt by targeting miR-21 and miR-21 could be a target molecule of curcumol for CRC treatment. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]