Bufotalin induces cell cycle arrest and cell apoptosis in human malignant melanoma A375 cells

Pan, Zhaohai; Qu, Chuanjun; Chen, Ying; Chen, Xiaoyu; Liu, Xiaona; Wu, Hao; Xu, Wei; Ye, Lei; Lu, Peng; Li, Defang; Zheng, Qiusheng

doi:10.3892/or.2019.7032

Cited by 20 publications

(26 citation statements)

References 24 publications

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“…After incubating for 24 h at 37 °C and 5% CO 2 incubator, different concentrations of ailanthone were added, and the cells were further cultured for another 24 h in the incubator. After incubation, the cells were stained, and cell morphology was assessed under a fluorescence microscope (DMI3000B, Leica, Leica Microsystems CMS GmbH) [19].…”

Section: Methodsmentioning

confidence: 99%

“…Cells (2 × 10 5 /well) were seeded into six-well plates and grown overnight, then exposed to different concentrations of ailanthone for 24 h. Cells were then carefully collected and analyzed for reaction with annexin V-FITC/PI (Cat no. CA1020, Solarbio) according to the kit instructions (Beijing Solarbio Science & Technology Co., Ltd., Beijing, China), and the green fluorescence from annexin V-FITC and red fluorescence from PI were analyzed using flow cytometry (FACSCanto II, Becton, Dickinson and Company, New Jersey, USA) [19].…”

Section: Methodsmentioning

confidence: 99%

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RETRACTED: Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells

Liu

Pan

et al. 2019

Biomolecules

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Malignant melanoma is the most lethal type of skin cancer. Previous studies have shown that ailanthone has potent antitumor activity in a variety of cell lines. However, the anti-tumor effect of ailanthone on malignant melanoma remains unclear. To investigate the anti-tumor mechanisms of ailanthone in human melanoma B16 and mouse melanoma A375 cells, the cell counting kit-8 assay, colony formation assay, DNA content analysis, Hoechst 33258, and Annexin V-FITC/PI staining were used to assess cell proliferation, cell cycle distribution, and cell apoptosis, respectively. Western blotting was performed to evaluate the expression of cell cycle- and apoptosis-related proteins and regulatory molecules. The results showed that ailanthone significantly inhibited melanoma B16 and A375 cell proliferation as well as remarkably induced cell cycle arrest at the G0–G1 phase in B16 cells and the G2–M phase in A375 cells in a dose-dependent manner. Further investigation revealed that ailanthone promoted the expression of p21 and suppressed the expression of cyclin E in B16 cells or cyclin B in A375 cells through the PI3K-Akt signaling pathway. In addition, ailanthone induced B16 and A375 cell apoptosis via a caspase-dependent mechanism. Further studies showed that ailanthone remarkably downregulated Bcl-2 and upregulated Apaf-1 and Bax, and subsequently increased mitochondrial membrane permeabilization and released cytochrome c from the mitochondria in B16 cells and A375 cells. Taken together, ailanthone induces cell cycle arrest via the PI3K-Akt signaling pathway as well as cell apoptosis via the mitochondria-mediated apoptotic signaling pathway. Ailanthone may be potentially utilized as an anti-tumor agent in the management of malignant melanoma.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

RETRACTED: Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells

Liu

Pan

et al. 2019

Biomolecules

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“…Interestingly, frondoside A(frA), extracted from sea cucumber Cucumaria okhotensis, changed not only autophagy relating proteins such as LC3B-I/II but apoptosis relating proteins in BL cells [60]. Cinobufotalin, known to one of toad venom components has been reported to have anticancer effects in various cancer cell lines including esophageal squamous cell carcinoma and the melanoma cell line [63,64]. This anticancer effect was also observed in U937-a lymphoma cell line [59].…”

Section: Animal-derived Compounds and Lymphomamentioning

confidence: 99%

Review of Natural Compounds for the Management and Prevention of Lymphoma

et al. 2020

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Lymphoma is a type of blood cancer that can be categorized into two types-Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL). A total of 509,590 and 79,990 cases of NHL and HL were newly diagnosed in 2018, respectively. Although conventional therapy has stridden forward over recent decades, its adverse effects are still a hurdle to be solved. Thus, to help researchers develop better lymphoma treatment, this study aims to review the systematic anticancer data for natural products and their compounds. A variety of natural products showed anticancerous effects on lymphoma by regulation of intracellular mechanisms including apoptosis as well as cell cycle arrest. As these results shed light on the potential to substitute conventional therapy with natural products, it may become a promising strategy for lymphoma treatment in the near future.

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“…over the years, an enormous amount of evidences have accumulated in vitro and in vivo, suggesting that CGs are also effective in the prevetion and/or treatment of proliferative diseases, such as cancer [46,47]. CGs have inhibitory effects on lung cancer [48][49][50][51], melanoma [22,52], hepatocellular carcinoma [53,54], glioblastoma [55], breast cancer [36,37] [38], prostate cancer cells proliferation [56-58] and colon cancer [59,60]. However, the mechanism of inhibition have not yet been clear realized.…”

mentioning

confidence: 99%

“…Paradoxically, the expression of Nur77 is required for apoptotic effect of numerous apoptotic stimuli, including chemotherapeutic agents [18,20]. Mechanistically, the mitogenic and survival effect of Nur77 appears to be dependent on its transcription regulation in the nuclear, while its pro-apoptotic effect involves its translocation from the nucleus to the cytoplasm [15,16,[21][22][23][24][25]. Anti-cancer effect of many compounds is related to the apoptotic pathway after nuclear translocation of Nur77 [11, 12, 14-16, 23, 26-32].…”

mentioning

confidence: 99%

10-4-4, A Cardiac Glycoside Block Growth in Cancer Cells via Nuclear Receptor Nur77 Mediated Na+/K+- ATPase Endocytosis

Bao

et al. 2021

Preprint

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Background Cancer is second only to heart disease as a cause of death. Develop new and more effective treatment strategies for cancer remain a major challenge for human medicine today. Nur77, an orphan member for the nuclear receptor superfamily, inhibits growth in cancer cells by translocation to cytoplasmic. Small molecules that trigger Nur77 nuclear export may be an ideal anti-cancer candidate. Methods Cell proliferation was evaluated by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The protein expression level were detected by western blot analysis. Immunostaining and cell fractionation assays were used to assess subcelluar localization of Nur77. Cell apoptosis, cell cycle and calcium were detected by flow cytometry. Zebrafish liver cancer models were used to determine anti-cancer effect of 10-4-4 in vivo. Results In this study, we exhibit 10-4-4 a cardiac glycoside, extracted from Antiaris toxicaria lesch, has sensitivity to cancer cells. 10-4-4 induces apoptosis and G2/M cell cycle arrest in HepG2 cells. Consistently, 10-4-4 augments Nur77 expression and cytoplasmic localization, its restraint of cancer cells growth is Nur77 dependent. Meanwhile, as a cardiac glycoside, 10-4-4 inhibits Na+/K+- ATPase (NaK) activation. To further confirm the molecular mechanism of 10-4-4, we found the association between Nur77 and NaK. The suppression of NaK by 10-4-4 increases the level of intracellular Ca2+. Ca2+, as a second messenger, specific activates protein kinase C (PKC). PKC has been reported on the influence of Nur77 nuclear export. Identical conclusions are obtained in this studies that 10-4-4 induces PKC activation play an important role in Nur77 nuclear export. Notably, the cytoplasmic Nur77 induced by 10-4-4 interaction with NaK to induce NaK endocytosis, and then trigger G2/M cell cycle arrest and apoptosis. Studies in Zebrafish shows that 10-4-4 potently inhibits the growth of liver cancer cells in vivo. Conclusions Our results exhibit that 10-4-4 possesses an anti-cancer activity in vitro and in vivo via NaK-Nur77 signaling pathway and maybe offers a novel strategy in development of chemotherapeutic anti-cancer drug.

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Bufotalin induces cell cycle arrest and cell apoptosis in human malignant melanoma A375 cells

Cited by 20 publications

References 24 publications

RETRACTED: Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells

RETRACTED: Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells

Review of Natural Compounds for the Management and Prevention of Lymphoma

10-4-4, A Cardiac Glycoside Block Growth in Cancer Cells via Nuclear Receptor Nur77 Mediated Na+/K+- ATPase Endocytosis

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