br In conclusion cytotoxic ketocholesterol and cholestane tr
In conclusion, cytotoxic 7-ketocholesterol and cholestane-3β-5α-6β-triol could act on SMO and LXRα pathways to promote cell death. In view of these findings, their potential pharmacological utility merit further investigation.
CRediT authorship contribution statement
Debora Levy: Conceptualization, Methodology, Investigation, Data curation, Formal analysis, Writing - original draft, Writing - review & editing. Thatiana Correa de Melo: Investigation, Data curation, Writing - review & editing. Beatriz A. Oliveira: Investigation, Data curation, Writing - review & editing. Jessica L. Paz: Investigation, Data curation, Writing - review & editing. Fabio A. de Freitas: Formal analysis, Writing - review & editing. Cadiele O. Reichert: Formal analysis, Writing - review & editing. Alessandro Rodrigues: Formal analysis, Writing - original draft, Writing - review & editing. Sergio P. Bydlowski: Conceptualization, Methodology, Formal analysis, Writing - original draft, Writing - review & editing, Supervision.
This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Instituto Nacional de Ciência e Tecnologia – Fluidos Complexos (INCT-FCx); Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa (INCT-Regenera), and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP – 13/10073-5 and 16/21676-0), all from Brazil.
Competing financial interests
The authors declare no competing financial interests
Appendix A. Transparency document
 T. Nury, A. Zarrouk, A. Vejux, et al., Induction of oxiapoptophagy, a mixed mode of cell death associated with oxidative stress, apoptosis and autophagy, on 7-ke-tocholesterol-treated 158N murine oligodendrocytes: impairment by alpha-toco-pherol, Biochem. Biophys. Res. Commun. 446 (2014) 714–719.
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European Journal of Pharmacology
journal homepage: www.elsevier.com/locate/ejphar
Full length article
8-Acetonyldihydronitidine inhibits the proliferation of human colorectal cancer Pyocyanin via activation of p53
Jiawang Zhoua, Ziqian Lia, Junjie Zhanga, Hongsheng Wanga, Sheng Yinb, Jun Dua,c,∗ a Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
b Lab of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
c School of Traditional Dai-Thai Medicine West Yunnan University of Applied Science, Yunnan, 666100, China
Cell cycle arrest
Colorectal cancer cells
8-Acetonyldihydronitidine (8-AHN) is a potent antitumor compound extracted from Toddalia asiatica. However, the precise molecular antitumor mechanisms of 8-AHN have not been well elucidated. Here, we showed that 8-AHN significantly inhibited the proliferation of human colorectal cell lines via induction of G2/M cell cycle arrest and apoptosis. We found that the p53 played a central role in 8-AHN-induced cell proliferation inhibition. Mechanistically, 8-AHN induced p53 expression and enhanced transcriptional activity, subsequently elevating the expression of p53 target genes, including p21, FAS, and BAX, and then increased the level of activated caspase-3 and decreased the level of cyclin B and cyclin A. Moreover, pifithrin-α, the p53 inhibitor, markedly reversed the above responses induced by 8-AHN, and small interfering RNA-mediated knockdown of TP53 also significantly decreased 8-AHN-induced cell apoptosis. The experiments in vivo showed that 8-AHN significantly suppressed the growth of HCT116 xenograft tumors, associated with proliferation suppression and apoptosis induction in tumor tissues, without inducing any notable major organ-related toxicity. In summary, 8-AHN displays an antitumor eﬀect through cell cycle arrest and apoptosis in colorectal cells via activating p53, which suggests that 8-AHN, exerted a therapeutic potential against colorectal cancer cells, and may be regarded as an eﬀective lead compound.