Cinobufacini from the Skin of <i>Bufo bufo gargarizans</i> Induces Apoptosis, Possibly via Activation of the Wnt/β-Catenin Pathway, in Human Osteosarcoma Cells

Ma, Xiucai; Ding, Huaiyu; Shi, Jiandang; Hei, Long; Niu, Ningkui; Suo, Zhigang; Shang, Yan-bing; Lin, Song; Pu, Feifei; Shao, Zengwu

doi:10.1177/1934578x1801300221

Cited by 2 publications

(4 citation statements)

References 24 publications

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“…This study showed that AB23A in combination with bufalin increased β-catenin protein, while decreased GSK-3β in LC cell strains (SMMC-7721 and MHCC97), suggesting the ability of AB23A and bufalin to activate the Wnt/β-catenin axis. The results were similar to the previous studies that AB23A activates the Wnt/β-catenin axis in human osteosarcoma cells by downregulating GSK-3β and upregulating β-catenin [20].…”

Section: Discussionsupporting

confidence: 92%

“…Abnormal activation of the Wnt/β-catenin axis has a close connection with the development of many human tumors like prostate can-cer [43,44]. Ma et al reported that AB23A induced human osteosarcoma cell apoptosis through Wnt/β-catenin signal activation [20]. However, the impacts of AB23A+bufalin on the Wnt/β-catenin axis in LC cells have not been studied so far.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the Wnt/β-catenin axis has been demonstrated to have a close connection with the biological processes involved in cancer [18,19]. Recently, AB23A has been reported to induce human osteosarcoma cell apoptosis through Wnt/ β-catenin signal activation [20]. However, the research regarding the involvement of bufalin or AB23A in LC via the Wnt/β-catenin axis remains scarce.…”

Section: Introductionmentioning

confidence: 99%

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Alisol B 23-Acetate Increases the Antitumor Effect of Bufalin on Liver Cancer through Inactivating Wnt/β-Catenin Axis

Tang

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. Liver cancer seriously threatens the health of people. Meanwhile, it has been reported that bufalin could act as an inhibitor in liver cancer. In addition, alisol B 23-acetate is a natural product derived from Alisma plantago-aquatica Linn which has an antitumor effect. In this study, we aimed to explore whether alisol B 23-acetate could increase the antitumor effect of bufalin on liver cancer. Methods. In order to detect the effect of alisol B 23-acetate in combination with bufalin on liver cancer, human liver cancer SMMC-7721 and MHCC97 cells were used as subjects. Bufalin and alisol B 23-acetate were performed on cells. Cell viability was tested by MTT assay. In addition, flow cytometry was performed to assess the cell apoptosis. Autophagy-related protein levels were tested by western blotting. Results. The data revealed that bufalin significantly decreased the viability of liver cancer cells, and the inhibitory effect was further increased by alisol B 23-acetate. In addition, alisol B 23-acetate notably enhanced the apoptotic effect of bufalin on liver cancer cells through mediation of Mcl-1, Bax, Bcl-2, and cleaved caspase-3. Meanwhile, alisol B 23-acetate in combination with bufalin induced the autophagy in liver cancer cells through mediation of Beclin-1 and p62. Furthermore, alisol B 23-acetate in combination with bufalin significantly downregulated the level of GSK-3β and increased the expression of β-catenin in liver cancer cells. Conclusion. In summary, these findings provide the first evidence that alisol B 23-acetate improves the anticancer activity of bufalin on liver cancer through activation of the Wnt/β-catenin axis, and these outcomes might shed new lights on exploring the new methods against liver cancer.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alisol B 23-Acetate Increases the Antitumor Effect of Bufalin on Liver Cancer through Inactivating Wnt/β-Catenin Axis

Tang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Cinobufacini injection (CI), extracted from the skin of the Bufo bufo gargarizans Cantor, has the effects on clearing away heat and toxic material, inducing diuresis for removing edema. CI has been broadly used for clinical cancer treatment [9], including OS [10,11], but the pharmacological mechanisms governing these processes remains unknown, which limits its clinical application and promotion.…”

Section: Introductionmentioning

confidence: 99%

Cinobufacini Injection Suppresses the Proliferation of Human Osteosarcoma Cells by Inhibiting PI3K/Akt Signaling Pathway

Chen

Zhai

Chen

et al. 2021

Preprint

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Background: Cinobufacini injection (CI), an aqueous extraction from the Cutis Bufonis, is broadly used in clinical treatment of cancer in China. However, the underlying molecular mechanisms of CI in treating osteosarcoma (OS) remain unclear. Aberrant activation of PI3K-AKT signaling pathway is the cause of many types of cancer, including OS. Therefore, we investigated the effect of CI on proliferation, apoptosis and cell cycle of OS cells and elucidated the molecular mechanism of CI in inhibiting OS cells. Methods: Cell proliferation of U2OS and MG63 cells after CI treatment was measured by CCK-8 assay, colony formation and morphological changes. Additionally, the cell cycle arrest and apoptosis induced by CI, were determined by FACS and Western blot analysis. The mechanisms of CI on OS were evaluated by RNA-seq and Western blot analysis. Results: We founf that CI reduced the proliferation of U2OS and MG63 cells in a dose- and time- dependent manner. Furthermore, CI induced the U2OS cells cycle arrest in G0/G1 phase, but the MG63 cells cycle arrest in G2/M phase. Consequently, CI triggered the apoptosis in both OS cells, with enhanced caspase-3 activity and decreased expression of Bcl-2/Bax. In addition, RNA-seq data indicated that PI3K-Akt signaling pathway played an essential role in CI treatment. Moreover PI3K and phosphorylation of AKT (p-AKT) were significantly down-regulated by CI in both OS cells. Conclusions: These results indicate that CI significantly inhibited the proliferation, induced the cell cycle arrest, as well as apoptosis in human OS cells, which is mediated by the inactivation of PI3K-Akt signaling pathway. These findings suggest that CI may have potential for the treatment of OS.

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Cinobufacini from the Skin of Bufo bufo gargarizans Induces Apoptosis, Possibly via Activation of the Wnt/β-Catenin Pathway, in Human Osteosarcoma Cells

Cited by 2 publications

References 24 publications

Alisol B 23-Acetate Increases the Antitumor Effect of Bufalin on Liver Cancer through Inactivating Wnt/β-Catenin Axis

Alisol B 23-Acetate Increases the Antitumor Effect of Bufalin on Liver Cancer through Inactivating Wnt/β-Catenin Axis

Cinobufacini Injection Suppresses the Proliferation of Human Osteosarcoma Cells by Inhibiting PI3K/Akt Signaling Pathway

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