Cytotoxic activity of broussochalcone a against colon and liver cancer cells by promoting destruction complex-independent β-catenin degradation

Shin, Sora; Son, Younglim; Liu, Kwang-Hyeon; Kang, Wonku; Oh, Sangtaek

doi:10.1016/j.fct.2019.05.058

Cited by 15 publications

(12 citation statements)

References 33 publications

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“…Brousschalcone has also been shown to modulate Wnt/β-catenin pathway function. Shin et al [ 142 ] found that this chalcone promoted the phosphorylation of β-catenin and reduced its levels by increasing its ubiquitination and degradation in the proteasome. Another feature of this chalcone action was the downregulation of the expression of β-catenin-dependent genes such as cyclin D1, c-Myc, axin2 and the activation of apoptosis-mediated proteins such as caspase 3/7 in liver and colon cancer cells.…”

Section: Modulation Of Selected Signaling Pathwaysmentioning

confidence: 99%

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Michalková¹,

Mirossay²,

Gazdova³

et al. 2021

Cancers

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Although great progress has been made in the treatment of cancer, the search for new promising molecules with antitumor activity is still one of the greatest challenges in the fight against cancer due to the increasing number of new cases each year. Chalcones (1,3-diphenyl-2-propen-1-one), the precursors of flavonoid synthesis in higher plants, possess a wide spectrum of biological activities including antimicrobial, anti-inflammatory, antioxidant, and anticancer. A plethora of molecular mechanisms of action have been documented, including induction of apoptosis, autophagy, or other types of cell death, cell cycle changes, and modulation of several signaling pathways associated with cell survival or death. In addition, blockade of several steps of angiogenesis and proteasome inhibition has also been documented. This review summarizes the basic molecular mechanisms related to the antiproliferative effects of chalcones, focusing on research articles from the years January 2015–February 2021.

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Section: Modulation Of Selected Signaling Pathwaysmentioning

confidence: 99%

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Michalková¹,

Mirossay²,

Gazdova³

et al. 2021

Cancers

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“…Recently, BCA was reported to be an inhibitor of the orphan nuclear receptor, NR4A1, and induces programmed cell death in pancreatic cancer cells [ 14 ]. Moreover, the cytotoxic effect of BCA against colorectal and liver cancer cells occurs via the accelerated destruction of complex-independent β -catenin degradation [ 32 ]. Furthermore, the inhibitory potential of BCA for the CYP2J2 isoform and its antitumor effects occur via FOXO3 activation [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, the results of cell cycle analysis revealed that G2/M cell cycle arrest was induced in renal cancer cells as BCA concentration increased ( Figure 2 ). BCA has been reported to induce apoptosis in SW480, HCT116, and SNU475 cells [ 32 ]. Herein, apoptotic cell death was detected in both A498 and ACHN cells ( Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

Broussochalcone A Induces Apoptosis in Human Renal Cancer Cells via ROS Level Elevation and Activation of FOXO3 Signaling Pathway

Lee

Cha

Nam

et al. 2021

Oxidative Medicine and Cellular Longevity

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Broussochalcone A (BCA) is a chalcone compound extracted from the cortex of Broussonetiapapyrifera (L.) Ventenat that exerts various effects, such as potent antioxidant, antiplatelet, and anticancer effects. However, the effects of BCA against cancers have been seldom studied. This study is aimed at demonstrating the apoptotic mechanisms of BCA in A498 and ACHN cells, which are two types of human renal cancer cell lines. MTT, cell counting, and colony formation assays indicated that BCA treatment inhibited cell viability and cell growth. Further, cell cycle analysis revealed that BCA induced cell cycle arrest at the G2/M phase. Annexin V/PI staining and TUNEL assays were performed to determine the apoptotic effects and DNA fragmentation after treatment with BCA. Based on western blot analysis, BCA induced the upregulation of cleaved PARP, FOXO3, Bax, p21, p27, p53, phosphorylated p53 (ser15, ser20, and ser46), and active forms of caspase-3, caspase-7, and caspase-9 proteins, but downregulated the proforms of the proteins. The expression levels of pAkt, Bcl-2, and Bcl-xL were also found to be downregulated. Western blot analysis of nuclear fractionation results revealed that BCA induced the nuclear translocation of FOXO3, which might be induced by DNA damage owing to the accumulation of reactive oxygen species (ROS). Elevated intracellular ROS levels were also found following BCA treatment. Furthermore, DNA damage was detected after BCA treatment using a comet assay. The purpose of this study was to elucidate the apoptotic effects of BCA against renal cancer A498 and ACHN cells. Collectively, our study findings revealed that the apoptotic effects of BCA against human renal cancer cells occur via the elevation of ROS level and activation of the FOXO3 signaling pathway.

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“…The Wnt/β-catenin pathway regulates both autophagy and apoptosis [36,37]. Autophagy plays important roles in the cellular homeostasis mechanism against various cellular stresses through autophagosome and lysosome system [38].…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Activity of Aplykurodin A Isolated From Aplysia kurodai against AXIN1-Mutated Hepatocellular Carcinoma Cells by Promoting Oncogenic β-Catenin Degradation

Lee

Zhou

et al. 2020

Marine Drugs

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Dysregulation of the Wnt/β-catenin signaling pathway is involved in the development of human hepatocellular carcinoma and has thus emerged as a therapeutic target for this malignant tumor. In this study, we employed sensitive cell-based assays to identify aplykurodin A isolated from Aplysia kurodai as an antagonist of Wnt/β-catenin signaling. Aplykurodin A inhibited β-catenin responsive transcription, which was stimulated by a Wnt3a-conditioned medium or a glycogen synthase kinase 3β inhibitor by accelerating intracellular β-catenin degradation. Aplykurodin A downregulated the level of oncogenic β-catenin and decreased the expression of β-catenin-dependent gene, leading to inhibition of human hepatoma Hep3B and SNU475 cell proliferation. Moreover, apoptosis and autophagy were elicited by aplykurodin A, as indicated by an increase the number of Annexin V-FITC-stained cells and the formation of microtubule-associated protein 1 light chain 3 puncta, respectively, in Hep3B and SNU475 cells. Our findings suggest that aplykurodin A provides a novel therapeutic strategy for human hepatocellular carcinoma via stimulation of oncogenic β-catenin degradation.

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Cytotoxic activity of broussochalcone a against colon and liver cancer cells by promoting destruction complex-independent β-catenin degradation

Cited by 15 publications

References 33 publications

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Broussochalcone A Induces Apoptosis in Human Renal Cancer Cells via ROS Level Elevation and Activation of FOXO3 Signaling Pathway

Cytotoxic Activity of Aplykurodin A Isolated From Aplysia kurodai against AXIN1-Mutated Hepatocellular Carcinoma Cells by Promoting Oncogenic β-Catenin Degradation

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