Cinobufagin induces FOXO1-regulated apoptosis, proliferation, migration, and invasion by inhibiting G9a in non-small-cell lung cancer A549 cells

Zhang, Lingling; Liang, Bing; Xu, Huan; Gong, Yanju; Hu, Wangming; Wu, Xiao; Chen, Xiongbin; Li, Min; Shi, Lei; Shi, Ya-Zhou; Wang, Yong; Yang, Lan

doi:10.1016/j.jep.2022.115095

Cited by 28 publications

(32 citation statements)

References 40 publications

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“…Cinobufagin: Bufadienolide cinobufagin, which is extracted from the Asiatic toad Bufo gargarizans, has analgesic, detoxifying, and detumescent properties[ 27 ]. Some investigations conducted recently have revealed that it has potent anti-tumor effects as well.…”

Section: Resultsmentioning

confidence: 99%

“…Some investigations conducted recently have revealed that it has potent anti-tumor effects as well. In non-small cell lung cancer, cinobufagin could suppress proliferation, migration, and invasion of cancer cells by inhibiting the expression of G9a[ 27 ]. By interfering with the cell cycle, cinobufagin also inhibits the survival of cancer cells and promotes apoptosis[ 28 ].…”

Section: Resultsmentioning

confidence: 99%

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Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment

Qin¹,

Feng²,

Zhang³

et al. 2022

World J Clin Cases

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BACKGROUND Ribonucleotide reductase (RR) is a key enzyme in tumor proliferation, especially its subunit-RRM2. Although there are multiple therapeutics for tumors, they all have certain limitations. Given their advantages, traditional Chinese medicine (TCM) monomers have become an important source of anti-tumor drugs. Therefore, screening and analysis of TCM monomers with RRM2 inhibition can provide a reference for further anti-tumor drug development. AIM To screen and analyze potential anti-tumor TCM monomers with a good binding capacity to RRM2. METHODS The Gene Expression Profiling Interactive Analysis database was used to analyze the level of RRM2 gene expression in normal and tumor tissues as well as RRM2's effect on the overall survival rate of tumor patients. TCM monomers that potentially act on RRM2 were screened via literature mining. Using AutoDock software, the screened monomers were docked with the RRM2 protein. RESULTS The expression of RRM2 mRNA in multiple tumor tissues was significantly higher than that in normal tissues, and it was negatively correlated with the overall survival rate of patients with the majority of tumor types. Through literature mining, we discovered that berberine, ursolic acid, gambogic acid, cinobufagin, quercetin, daphnetin, and osalmide have inhibitory effects on RRM2. The results of molecular docking identified that the above TCM monomers have a strong binding capacity with RRM2 protein, which mainly interacted through hydrogen bonds and hydrophobic force. The main binding sites were Arg330, Tyr323, Ser263, and Met350. CONCLUSION RRM2 is an important tumor therapeutic target. The TCM monomers screened have a good binding capacity with the RRM2 protein.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment

Qin¹,

Feng²,

Zhang³

et al. 2022

World J Clin Cases

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“…CB possesses various biological activities, such as cardiotonic, blood pressure stimulation, antineoplastic, analgesic, antiseptic and immunomodulator. [19,20] In particular, recent studies have revealed that CB exhibits cytotoxicity against various human cancer cell lines, such as colorectal cancer, [21] osteosarcoma, [22] breast cancer, [23] lung cancer, [4,24,25] gastric cancer, [26] melanoma, [27] liver cancer, [28] cholangiocarcinoma, [29] esophageal squamous cell carcinoma, [30] and nasopharyngeal carcinoma. [31] Most of the researches focused on the anti-proliferation, apoptosis inducing activity, cell cycle arrest effect of CB, and the mechanism mainly involved inhibition of AKT signaling pathway, mitochondrial dysfunction, Wnt/β-catenin signaling pathway inhibition, Notch signaling pathway inactivation, and spindle formation defection.…”

Section: Introductionmentioning

confidence: 99%

Effects of Cinobufagin on the Proliferation, Migration, and Invasion of H1299 Lung Cancer Cells

Sun

Huang

Liu

et al. 2023

Chemistry & Biodiversity

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Cinobufagin (CB), with its steroidal nucleus structure, is one of the major, biologically active components of Chan Su. Recent studies have shown that CB exerts inhibitory effects against numerous cancer cells. However, the effects of CB regarding the metastasis of non-small cell lung cancer (NSCLC) and the involved mechanisms need to be further studied. The purpose of the present study aimed to report the inhibitory function of CB against proliferation and metastasis of H1299 cells. CB inhibited proliferation of H1299 lung cancer cells with an IC 50 value of 0.035 � 0.008 μM according to the results of MTT assays. Antiproliferative activity was also observed in colony forming cell assays. In addition, 5-ethynyl-2'-deoxyuridine (EdU) retention assays revealed that CB significantly inhibited the rate of DNA synthesis in H1299 cells. Moreover, results of the scratch wound healing assays and transwell migration assays displayed that CB exhibited significant inhibition against migration and invasion of H1299 cells. Furthermore, CB could concentration-dependently reduce the expression of integrin α2, β-catenin, FAK, Src, c-Myc, and STAT3 in H1299 cells. These western blotting results indicated that CB might target integrin α2, β-catenin, FAK and Src to suppress invasion and migration of NSCLC, which was consistent with the network pharmacology analysis results. Collectively, findings of the current study suggest that CB possesses promising activity against NSCLC growth and metastasis.

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“…Cinobufotalin is a monomer from Bufo bufo gargarizans Cantor and Bufo melanostictus Schneider extracts used in traditional Chinese medicine ( Zhang et al, 2020 ). Cinobufagin, a primary component isolated from cinobufotalin, has been shown to exert antitumor effects on a number of malignant tumors such as hepatocellular carcinoma, colorectal cancer, lung cancer, and osteosarcoma ( Qi et al, 2011 ; Dai et al, 2018 ; Bai et al, 2021 ; Zhang et al, 2022 ). A previous study showed that cinobufagin attenuated bleomycin-induced pulmonary fibrosis in mice ( Li et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Cinobufagin alleviates lipopolysaccharide-induced acute lung injury by regulating autophagy through activation of the p53/mTOR pathway

Wang

Mei

et al. 2022

Front. Pharmacol.

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Acute lung injury (ALI) is a severe clinical disorder characterized by dysregulated inflammatory responses, leading to high rates of morbidity and mortality. Cinobufagin, a primary component isolated from cinobufotalin, exerts strong anticancer effects. However, there are few reports on its role in ALI, and it is unclear whether cinobufagin affects lipopolysaccharide (LPS)-induced ALI. Therefore, the present study aimed to investigate the effect of cinobufagin on LPS-induced ALI and to assess its potential mechanism of action. The results showed that cinobufagin alleviated lung histopathological changes and protected the permeability of lung tissues in LPS-induced ALI. In addition, cinobufagin effectively suppressed inflammatory responses through the induction of autophagy in LPS-induced ALI cells and in a mouse model. Moreover, cinobufagin enhanced autophagy through the p53/mTOR pathway in LPS-induced ALI. Herein, it was reported for the first time that cinobufagin inhibited the inflammatory response of LPS-induced ALI, which laid the foundation for further understanding and development of cinobufagin as a potential new drug for ALI.

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Cinobufagin induces FOXO1-regulated apoptosis, proliferation, migration, and invasion by inhibiting G9a in non-small-cell lung cancer A549 cells

Cited by 28 publications

References 40 publications

Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment

Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment

Effects of Cinobufagin on the Proliferation, Migration, and Invasion of H1299 Lung Cancer Cells

Cinobufagin alleviates lipopolysaccharide-induced acute lung injury by regulating autophagy through activation of the p53/mTOR pathway

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