Shikonin suppresses pulmonary fibroblasts proliferation and activation by regulating Akt and p38 MAPK signaling pathways

Nie, Yunjuan; Yang, Yeming; Zhang, Jian; Cai, Guowei; Chang, Yanhua; Chai, Gaoshang; Guo, Chongyong

doi:10.1016/j.biopha.2017.09.023

Cited by 26 publications

(21 citation statements)

References 52 publications

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“…It has been found that shikonin exhibits anti-proliferation and apoptosis-inducing effects on 4T1 murine mammary cancer and MDA-MB-231 human breast cancer cells (Figs. 1-3) (17,18). Various medicinal plants have been examined for anti-tumor compounds (19).…”

Section: Discussionmentioning

confidence: 99%

Shikonin induces an anti‑tumor effect on murine mammary cancer via p38‑dependent apoptosis

Koizumi

Liu

et al. 2019

Oncol Rep

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Breast cancer is the most common malignancy in women. Apoptosis is important for tumor suppression and may delay cancer progression. It was found that shikonin induced apoptosis in 4T1 murine mammary cancer cells and MDA-MB-231 human breast cancer cells in vitro. Total p38 and c-Jun N-terminal kinase (JNK) levels were maintained in 4T1 cells, and p38 phosphorylation, but not JNK phosphorylation, was significantly increased. Caspase-3/7 activity was detected, which suggested that the p38 pathway, but not the JNK signaling pathway, induced apoptosis in 4T1 cells. The anti-tumor effects of shikonin on orthotopic mouse models were also examined. On day 7 after inoculation of 4T1 cells into mice, tumor volumes in the shikonin-treated and the control groups began to differ. On day 13, tumors were weighed, and shikonin was revealed to suppress tumor growth in the orthotopic 4T1 model in vivo. In conclusion, shikonin is a potential anti-tumor drug for breast cancer.

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Section: Discussionmentioning

confidence: 99%

Shikonin induces an anti‑tumor effect on murine mammary cancer via p38‑dependent apoptosis

Koizumi

Liu

et al. 2019

Oncol Rep

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“…Mouse lung fibroblasts were obtained using a protocol as previously reported, with modification. Six to 8 weeks‐old mice were euthanized and the whole lungs were collected and cut into small pieces, minced, and then subjected to collagenase type IV and DNase I digestion (Sigma, St Louis, MO, USA) then placed in DMEM with 100 IU/mL penicillin‐streptomycin and 5% foetal bovine serum (FBS) for 30 minutes.…”

Section: Methodsmentioning

confidence: 99%

“…Mouse lung fibroblasts were obtained using a protocol as previously reported, 9 and 5% CO 2 for 7-14 days in DMEM supplemented with 10% FBS and penicillin/streptomycin. Tissue fragments were discarded and the cells used for analysis.…”

Section: Culture and Treatment Of Primary Mouse Lung Fibroblastsmentioning

confidence: 99%

“…Interestingly, those two key components of proliferation have also been identified as being adaptive for fibroblasts . Thus, suppression of proliferation of fibroblasts via the regulation of apoptosis and cell cycle progression is a pivotal therapeutic direction for pulmonary fibrosis …”

Section: Introductionmentioning

confidence: 99%

“…8 Thus, suppression of proliferation of fibroblasts via the regulation of apoptosis and cell cycle progression is a pivotal therapeutic direction for pulmonary fibrosis. 9 Additionally, pulmonary fibroblasts are capable of differentiation into myofibroblasts in response to profibrotic cytokines such as TGF-β1 during the process of wound healing leading to the development of pulmonary fibrosis and resulting in overproduction of extracellular matrix (ECM) including alpha smooth muscle actin (α-SMA), fibronectin and various collagen types. 10 Therefore, differentiation of fibroblasts is a second key process that occurs during the course of fibrosis.…”

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confidence: 99%

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Lanatoside C protects mice against bleomycin‐induced pulmonary fibrosis through suppression of fibroblast proliferation and differentiation

Nie

Zhang

Jin

et al. 2019

Clin Exp Pharma Physio

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Summary It has been established that lanatoside C, a FDA‐approved cardiac glycoside, reduces proliferation of cancer cell lines. The proliferation of fibroblasts is critical to the pathogenesis of pulmonary fibrosis (PF), a progressive and fatal fibrotic lung disease lacking effective treatment. In this study we have investigated the impact of lanatoside C on a bleomycin (BLM)‐induced mouse model of PF and through the evaluation of fibroblast proliferation and activation in vitro. We evaluated explanted lung tissue by histological staining, western blot analysis, qRT‐PCR and survival analysis, demonstrating that lanatoside C was able to protect mice against BLM‐induced pulmonary fibrosis. The proliferation of cultured pulmonary fibroblasts isolated from BLM‐induced PF mice was suppressed by lanatoside C, as hypothesized, through the induction of cell apoptosis and cell cycle arrest at the G2/M phase. The Akt signalling pathway was involved in this process. Interestingly, the production of α‐SMA, fibronectin, and collagen I and III in response to TGF‐β1 in healthy mouse fibroblasts was suppressed following lanatoside C administration by inhibition of TGF‐β1/Smad signalling. In addition, TGF‐β1‐induced migration in lung fibroblasts was also impeded after lanatoside C treatment. Together, our data revealed that lanatoside C alleviated BLM‐induced pulmonary fibrosis in mice via attenuation of growth and differentiation of fibroblasts, suggesting that it has potential as a candidate therapy for PF patients.

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Integrated multicomponent analysis based on UHPLC‐Q‐Exactive Orbitrap‐MS and network pharmacology to elucidate the potential mechanism of Baoyuan decoction against idiopathic pulmonary fibrosis

Zhang

Gao

et al. 2022

Phytochemical Analysis

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Introduction: Idiopathic pulmonary fibrosis (IPF) is a serious lung disease with a high mortality rate. Baoyuan decoction (BYD), a classic medicinal food homology recipe, has anti-apoptotic effects, enhances immune function, and alleviates fibrosis, suggesting that it may be a potential therapeutic drug for IPF.Objectives: We aimed to identify the main active ingredients of BYD, determine the basis of its efficacy, prove its anti-IPF effects, and explore the mechanisms underlying its anti-IPF effects. Materials and methods:In this study, the active components of BYD were detected and analysed by ultra-high-performance liquid chromatography coupled with hybrid quadrupole Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). A network pharmacology analysis was performed to determine the potential targets and relevant pathways of BYD in treating IPF. Western blotting and quantitative realtime polymerase chain reaction (qPCR) were conducted to verify the efficacy of BYD against IPF. Finally, molecular docking and qPCR were performed to identify the central targets of BYD.Results: A total of 39 components of BYD were identified. After performing the network pharmacology analysis, 35 active components and eight presumptive targets of BYD were found to play a central role in its anti-IPF effects. The molecular docking results indicated that most of the active components of BYD exhibited good binding activity with these eight central target proteins. In addition, the expression of collagen, α-SMA, and these eight targets in human pulmonary fibroblast (HPF) cells was suppressed from treatment with BYD. Conclusion:This study determined the efficacy of BYD against IPF and clarified its multiple-target and multiple-pathway mechanisms. Furthermore, the study also provides a new method for exploring the chemical and pharmacological bases of other traditional Chinese medicine (TCM).

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Shikonin suppresses pulmonary fibroblasts proliferation and activation by regulating Akt and p38 MAPK signaling pathways

Cited by 26 publications

References 52 publications

Shikonin induces an anti‑tumor effect on murine mammary cancer via p38‑dependent apoptosis

Shikonin induces an anti‑tumor effect on murine mammary cancer via p38‑dependent apoptosis

Lanatoside C protects mice against bleomycin‐induced pulmonary fibrosis through suppression of fibroblast proliferation and differentiation

Integrated multicomponent analysis based on UHPLC‐Q‐Exactive Orbitrap‐MS and network pharmacology to elucidate the potential mechanism of Baoyuan decoction against idiopathic pulmonary fibrosis

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