Cinobufagin, a bufadienolide, activates ROS-mediated pathways to trigger human lung cancer cell apoptosis in vivo

Peng, Panli; Lv, Junhong; Cai, Changqing; Lin, Shaohuan; Zhuo, Enqing; Wang, Senming

doi:10.1039/c7ra01085k

Cited by 12 publications

(5 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have shown that CB has potent cytotoxicity across a broad spectrum of cancer cell lines. It has been reported that CB has an inhibitory activity against NSCLC cell proliferation [4,25] . In this study, CB exhibited powerful cytotoxicity against H1299 cells.…”

Section: Discussionmentioning

confidence: 54%

“…It has been reported that CB has an inhibitory activity against NSCLC cell proliferation. [4,25] In this study, CB exhibited powerful cytotoxicity against H1299 cells. The IC 50 value was 0.035 � 0.008 μM, and the inhibition levels positively correlated with the concentrations (Figure 1).…”

Section: Discussionmentioning

confidence: 65%

“…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%

See 2 more Smart Citations

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

Sun

Huang

Liu

et al. 2023

Chemistry & Biodiversity

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Sun

Huang

Liu

et al. 2023

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

“…First, cinobufagin was selected as a candidate radioprotector as it may activate the ATM-CHK2 signaling pathway, which promotes DNA repair ( 32 ). Several studies have demonstrated that cinobufagin exerts anti-inflammatory ( 33 ), anti-bacterial ( 34 ), antitumor ( 35 , 36 ) and immune-enhancing effects ( 37 , 38 ). However, its clinical application is restricted by rapid metabolism and cardiotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Predictive DNA damage signaling for low‑dose ionizing radiation

Park,

Jung,

Song

et al. 2024

Int J Mol Med

View full text Add to dashboard Cite

Numerous studies have attempted to develop biological markers for the response to radiation for broad and straightforward application in the field of radiation. Based on a public database, the present study selected several molecules involved in the DNA damage repair response, cell cycle regulation and cytokine signaling as promising candidates for low-dose radiation-sensitive markers. The HuT 78 and IM-9 cell lines were irradiated in a concentration-dependent manner, and the expression of these molecules was analyzed using western blot analysis. Notably, the activation of ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (CHK2), p53 and H2A histone family member X (H2AX) significantly increased in a concentration-dependent manner, which was also observed in human peripheral blood mononuclear cells. To determine the radioprotective effects of cinobufagin, as an ATM and CHK2 activator, an in vivo model was employed using sub-lethal and lethal doses in irradiated mice. Treatment with cinobufagin increased the number of bone marrow cells in sub-lethal irradiated mice, and slightly elongated the survival of lethally irradiated mice, although the difference was not statistically significant. Therefore, KU60019, BML-277, pifithrin-α, and nutlin-3a were evaluated for their ability to modulate radiation-induced cell death. The use of BML-277 led to a decrease in radiation-induced p-CHK2 and γH2AX levels and mitigated radiation-induced apoptosis. On the whole, the present study provides a novel approach for developing drug candidates based on the profiling of biological radiation-sensitive markers. These markers hold promise for predicting radiation exposure and assessing the associated human risk.

show abstract

“…Previous studies have shown that cinobufagin reduced the expression of LEF1 and Wnt/β-catenin target genes such as Axin-2, cyclin D1, and c-Myc in melanoma cell lines [ 50 ], and cinobufagin treatment reduced the expression of p-AKTT308 and p-AKTS473 and inhibited the AKT/mTOR signaling pathway in human non-small cell lung cancer (NSCLC) cells [ 51 ]. In addition, cinobufagin effectively induced apoptosis in A549 cells by triggering caspase activation through both intrinsic and extrinsic pathways [ 52 ]. In colorectal cancer, cinobufagin inhibited proliferation, migration, invasion and promoted apoptosis of HCT116, RKO and SW480 cells.…”

Section: Discussionmentioning

confidence: 99%

Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1

Yang

Lee

et al. 2021

IJMS

View full text Add to dashboard Cite

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including oral squamous cell carcinoma (OSCC). OSCC is a highly aggressive cancer and the most common oral malignancy. ANO1 has been proposed as a potential candidate for targeted anticancer therapy. In this study, we performed a cell-based screening to identify novel regulators leading to the downregulation of ANO1, and discovered cinobufagin, which downregulated ANO1 expression in oral squamous cell carcinoma CAL-27 cells. ANO1 protein levels were significantly reduced by cinobufagin in a dose-dependent manner with an IC50 value of ~26 nM. Unlike previous ANO1 inhibitors, short-term (≤10 min) exposure to cinobufagin did not alter ANO1 chloride channel activity and ANO1-dependent intestinal smooth muscle contraction, whereas long-term (24 h) exposure to cinobufagin significantly reduced phosphorylation of STAT3 and mRNA expression of ANO1 in CAL-27 cells. Notably, cinobufagin inhibited cell proliferation of CAL-27 cells expressing high levels of ANO1 more potently than that of ANO1 knockout CAL-27 cells. In addition, cinobufagin significantly reduced cell migration and induced caspase-3 activation and PARP cleavage in CAL-27 cells. These results suggest that downregulation of ANO1 by cinobufagin is a potential mechanism for the anticancer effect of cinobufagin in OSCC.

show abstract

Cinobufagin, a bufadienolide, activates ROS-mediated pathways to trigger human lung cancer cell apoptosis in vivo

Abstract: Lung cancer, as the most common malignancy worldwide, is one of the most threatening diseases for human beings.

Cited by 12 publications

References 53 publications

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

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

Predictive DNA damage signaling for low‑dose ionizing radiation

Cinobufagin Exerts Anticancer Activity in Oral Squamous Cell Carcinoma Cells through Downregulation of ANO1

Contact Info

Product

Resources

About