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Anticancer effects of liriodenine on the cell growth and apoptosis of human breast cancer MCF-7 cells through the upregulation of p53 expression.

ABSTRACT: Liriodenine has wide pharmacological functions in phytochemistry, pharmacology and antitumor activities. The anticancer effects of liriodenine on the cell growth and apoptosis of human breast cancer MCF-7 cells, and the underlying mechanisms, are yet to be elucidated. Therefore, the present study investigated the anticancer effects of liriodenine on the cell growth and apoptosis of human breast cancer MCF-7 cells. We used MTT assay to measure cell growth, and flow cytometer and DAPI staining was used to analyze cell apoptosis. Then, Western blot analysis was executed to measure B-cell lymphoma-2 protein (Bcl-2), cyclin D1, vascular endothelial growth factor (VEGF), and p53 protein expression. The effect of liriodenine induced significant apoptosis and suppression of cell growth of the MCF-7 cells. Furthermore, the potential mechanism underlying its antitumor effect on MCF-7 cells may result from activation of caspase-3 activity, Bcl-2, cyclin D1 and VEGF, and promotion of p53 protein expression in MCF-7 cells. Therefore, the present results indicated that the anticancer effects of liriodenine suppress cell growth and induce the apoptosis of human breast cancer MCF-7 cells through inhibition of Bcl-2, cyclin D1 and VEGF expression, and upregulation of p53 expression. Therefore, liriodenine may be a potential therapy for the treatment of human breast cancer.

SUBMITTER: Li ZH

PROVIDER: S-EPMC5530144 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:Melanoma, one of the most lethal forms of skin cancer, has the potential to develop in any area where melanocytes are present. Currently, postoperative recurrence due to the emergence of systemic drug resistance represents a significant challenge in the treatment of melanoma. In this study, terphenyllin (TER), a distinctive inhibitory impact on melanoma cells was identified from the natural p-terphenyl metabolite. This study aimed to elucidate the intrinsic mechanism of this inhibitory effect, which may facilitate the discovery of novel chemotherapeutic agents. A transcriptome sequencing and metabolomic analysis of TER-treated A375 cells was conducted to identify potential pathways of action. The key proteins were knocked out and backfilled using CRISPR-Cas9 technology and molecular cloning. Subsequently, the results of cytosolic viability, LDH release, immunofluorescence and flow cytometry were employed to demonstrate the cell death status of the drug-treated cells. The p53 signalling pathway was markedly upregulated following TER treatment, leading to the activation of CASP3 via the intrinsic apoptotic pathway. The activated CASP3 initiated apoptosis, while simultaneously continuing to cleave the GSDME, thereby triggering pyroptosis. The knockout of p53, a key protein situated upstream of this pathway, resulted in a significant rescue of TER-induced cell death, as well as an alleviation of the decrease in cell viability. However, the knockout of key proteins situated downstream of the pathway (CASP3 and GSDME) did not result in a rescue of TER-induced cell death, but rather a transformation of the cells from apoptosis and pyroptosis. The induction of apoptosis and pyroptosis in A375 cells by TER is mediated via the p53-BAX/FAS-CASP3-GSDME signalling pathway. This lays the foundation for TER as a potential anti-melanoma drug in the future. It should be noted that CASP3 and GSDME in this pathway solely regulate the mode of cell death, rather than determine whether cell death occurs. This distinction may prove valuable in future studies of apoptosis and pyroptosis.

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Anticancer effects of liriodenine on the cell growth and apoptosis of human breast cancer MCF-7 cells through the upregulation of p53 expression.

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