Systems pharmacology unravels the synergic target space and therapeutic potential of Rhodiola rosea L. for non-small cell lung cancer.

Published on Dec 1, 2020in Phytomedicine4.268
· DOI :10.1016/J.PHYMED.2020.153326
Xia Zhang1
Estimated H-index: 1
(MOE: Chinese Ministry of Education),
Jinglin Zhu6
Estimated H-index: 6
(MOE: Chinese Ministry of Education)
+ 8 AuthorsYonghua Wang37
Estimated H-index: 37
(MOE: Chinese Ministry of Education)
Abstract Background Lung cancer is the most common and mortal cancer worldwide. Rhodiola rosea L. (RR), a well-known traditional Chinese medicine (TCM), has been turned out to be effective in anti-lung cancer therapy, but its molecular mechanism of action has not been clearly understood. Purpose In this study, we aimed to elucidate the possible molecular mechanism underlying the effect of RR against non-small cell lung cancer (NSCLC) by systems pharmacology. Methods The effects of RR on NSCLC were examined in Lewis lung carcinoma (LLC) tumor-bearing mice models. The possible molecular mechanism was unraveled by systems pharmacology, which includes pharmacokinetics evaluation, active compounds screening, target prediction and network analysis. Cell proliferation was examined by cell counting kit-8 (CCK-8) assay; cell apoptosis was detected by flow cytometry; protein and proinflammatory cytokines expression were evaluated by Western blot and qRT-PCR. Results In vivo, RR significantly inhibited the tumor growth and prolonged the survival of the tumor bearing mice. In silico, we identified 19 potential active molecules (e.g., salidroside and rhodiosin), 112 targets (e.g., COX-2 and AKT) and 27 pathways (e.g., PI3K/AKT signaling pathway and NF-κB signaling pathway) for RR. Additionally, targets analysis and networks construction further revealed that RR exerted anti-cancer effects by regulating apoptosis, angiogenesis and inflammation. In vitro, salidroside could significantly decrease expression of pro-angiogenic factors (e.g., VEGF and eNOS) and proinflammatory cytokines (e.g., COX-2, iNOS and TNF-α). Also, Bcl-2, an anti-apoptotic protein was decreased whereas Bax, a pro-apoptotic protein, was increased. Further flow cytometry analysis showed that salidroside could induce apoptosis in H1975 cells. Conclusions Mechanistically, the antitumor effect of RR on NSCLC was responsible for the synergy among anti-inflammatory, anti-angiogenic and pro-apoptotic.
📖 Papers frequently viewed together
3 Citations
5 Authors (Ge Yu, ..., Xiao‑Ling Feng)
17 Citations
#1R.Y. Tay (National Health Service)H-Index: 1
Last. Fiona H BlackhallH-Index: 69
view all 13 authors...
ABSTRACT Background The clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis of the prevalence and prognostic value of CTCs in LS-SCLC patients enrolled within the phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial. Patients and methods Baseline blood samples were enumerated for CTCs using CellSearch in 75 patients with LS-SCLC who were ...
27 CitationsSource
#1Alexander PanossianH-Index: 32
#2Ean-Jeong Seo (University of Mainz)H-Index: 17
Last. Thomas Efferth (University of Mainz)H-Index: 94
view all 3 authors...
Abstract Introduction The adaptogens modulate expression of genes playing key roles in development of aging-related disorders, which are considered as low-grade systemic inflammatory conditions characterized by an imbalance between pro-and anti-inflammatory eicosanoids. Aim of the Study We compared the effects of anti-inflammatory and adaptogenic plant extracts on the expression of genes involved in biosynthesis of eicosanoids with the purpose to find those plants, which selectively upregulated ...
16 CitationsSource
#1Mei RenH-Index: 1
#2Wenjing XuH-Index: 1
Last. Tao Xu (Qingdao University)H-Index: 1
view all 3 authors...
AbstractSalidroside, a glycoside of tyrosol, is isolated from Rhodiola rosea and shows anti-cancer functions in several cancers. However, the potentials of salidroside in the migration and invasion of lung cancer cells and its underlying mechanisms remain unknown. We aimed to investigate the functions and mechanisms of salidroside in non-small cell lung cancer (NSCLC). Human NSCLC cell line A549 was treated with different doses of salidroside. Cell viability, colony formation, apoptosis, migrati...
10 CitationsSource
#1Yanli Zhang (MUC: Minzu University of China)H-Index: 1
#2Xuewei Zhang (MUC: Minzu University of China)H-Index: 1
Last. Min Zhang (MUC: Minzu University of China)H-Index: 1
view all 5 authors...
Objective To explore the anti-tumor immune function of the Tibetan medicine Rhodiola rosea L. (RRL). Methods Lewis lung cancer-bearing mice were randomly divided into normal saline group, 500 mg/kg RRL ethanol extract treatment group, and 10 mg/kg cyclophosphamide (CTX) treatment group. All the groups underwent the treatment for 10 days. The mouse survival rate and tumor inhibitory rate were calculated. Additionally, the numbers of CD4+T and CD8+ T cells of tumor infiltrating lymphocytes as well...
3 Citations
#1Xing Su (Shihezi University)H-Index: 3
#2Yueping Li (Shihezi University)H-Index: 1
Last. Yonghua Wang (Shihezi University)H-Index: 37
view all 10 authors...
Abstract Non-small cell lung cancer (NSCLC) has become one of the most general malignancies in the world and has been shown to be the leading cause of cancer-related deaths. Traditional Chinese medicine (TCM) is considered to be a useful medicine for survival, and has been used in Asia for thousands of years. Hedyotis diffusa Willd (HDW) is an important folk herb that is used in clinical treatment of various cancers in various Chinese medicine prescriptions. However, its underlying mechanism of ...
18 CitationsSource
#1Shuna Cui (YZU: Yangzhou University)H-Index: 2
#2Qingqing Wu (YZU: Yangzhou University)H-Index: 3
Last. Shihua Li (YZU: Yangzhou University)H-Index: 2
view all 6 authors...
ABSTRACTThe natural flavonoid quercetin has antioxidant, anti-inflammatory, and anticancer effects. We investigated the effect of quercetin on lipopolysaccharide (LPS)-induced macrophage migration. Quercetin significantly attenuated LPS-induced inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) production in RAW264.7 cells without affecting their viability. Additionally, quercetin altered the cell size and induced an elongated morphology and enlarged the vacuoles and concentrated n...
23 CitationsSource
#1Jianling Liu (MOE: Chinese Ministry of Education)H-Index: 10
#2Meng Jiang (MOE: Chinese Ministry of Education)H-Index: 3
Last. Yonghua Wang (MOE: Chinese Ministry of Education)H-Index: 37
view all 11 authors...
Non-small cell lung cancer (NSCLC) is the most ordinary type of lung cancer which leads to 1/3 of all cancer deaths. At present, the cytotoxic chemotherapy, surgical resection, radiation and photodynamic therapy are the main strategies for NSCLC treatment. However, NSCLC are relatively resistant to the above therapeutic strategies, resulting in a rather low (20%) 5-year survival rate. Therefore, there is an urgent need to identify or develop efficient lead compounds for the treatment of NSCLC. H...
14 CitationsSource
#1Qiuli Liu (Third Military Medical University)H-Index: 7
#2Dali Tong (Third Military Medical University)H-Index: 8
Last. Jun Jiang (Third Military Medical University)H-Index: 10
view all 16 authors...
Purpose: Inflammatory infiltration plays important roles in both carcinogenesis and metastasis. We are interested in understanding the inhibitory mechanism of metformin on tumor-associated inflammation in prostate cancer. Experimental Design: By using TRAMP mouse model, in vitro macrophage migration assays, and patient samples, we examined the effect of metformin on tumor-associated inflammation during the initiation and after androgen deprivation therapy of prostate cancer. Results: Treating TR...
40 CitationsSource
#1Naveed Ishaque (DKFZ: German Cancer Research Center)H-Index: 21
#2Mohammed Abba (Heidelberg University)H-Index: 13
Last. Heike Allgayer (Heidelberg University)H-Index: 52
view all 26 authors...
Incomplete understanding of the metastatic process hinders personalized therapy. Here we report the most comprehensive whole-genome study of colorectal metastases vs. matched primary tumors. 65% of somatic mutations originate from a common progenitor, with 15% being tumor- and 19% metastasis-specific, implicating a higher mutation rate in metastases. Tumor- and metastasis-specific mutations harbor elevated levels of BRCAness. We confirm multistage progression with new components ARHGEF7/ARHGEF33...
47 CitationsSource
#1Jing HuH-Index: 1
#2LiBin ZhangH-Index: 1
Last. Tao ShouH-Index: 1
view all 9 authors...
: Cytoplasmic polyadenylation element binding protein 4 (CPEB4) could be an important regulator in variety of cancers. However, the biological function and the underlying molecular mechanism of CPEB4 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the metastasis role of CPEB4 in NSCLC cells, we knocked down CPEB4 using siRNA. Transwell migration assay and cell invasion assay on Matrigel were presented, and cell migration was also determined by scratch-healin...
9 CitationsSource
Cited By2
#1Xiaohan Wei (Southern Medical University)
#2Zhejun Zhao (Southern Medical University)
Last. Xiaomei Tan (Southern Medical University)H-Index: 8
view all 4 authors...
Abstract null null Ethnopharmacological relevance null Herbacetin is an active constituent of traditional Chinese medicines such as Ephedra sinica Stapf (MaHuang) and Sedum roseum (L.). Scop. (Hong JingTian). MaHuang was used to treat cough, asthma, fever, and edema for more than 5000 years, while Hong JingTian was used to treat depression, fatigue, cancers, and cardiovascular disease. Recent studies indicate that herbacetin and its glycosides play a critical role in the pharmacological activiti...