Raddeanin A inhibits growth and induces apoptosis in human colorectal cancer through downregulating the Wnt/β-catenin and NF-κB signaling pathway

Wang, Yu; Bao, Xiaowen; Zhao, Ang; Jie, Zhang; Zhang, Mingya; Zhang, Qi; Ma, Bo

doi:10.1016/j.lfs.2018.06.035

Cited by 27 publications

(21 citation statements)

References 55 publications

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“…While supporting the anticancer activity of RA that has been indicated in other cancer types, [19][20][21][22][23][24][25][26][27][28] our findings unveil a tissuespecific effect of RA in prostate cancer. That is to target AR-FL and AR-Vs.…”

Section: Discussionsupporting

confidence: 84%

“…18 Preclinical studies have indicated the antitumour activity of RA against gastric cancer, colorectal cancer, breast cancer, liver cancer, choriocarcinoma, glioblastoma and osteosarcoma. [19][20][21][22][23][24][25][26][27][28] In the present study, we sought to investigate the anticancer effect of RA in prostate cancer. We found that it could suppress the activity of both AR-FL and AR-Vs to inhibit the growth of prostate cancer cells at an in vivo achievable concentration.…”

mentioning

confidence: 99%

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Raddeanin A down‐regulates androgen receptor and its splice variants in prostate cancer

Xia

Bai

et al. 2019

J Cellular Molecular Medi

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Castration‐resistant progression of prostate cancer is a major cause of prostate cancer mortality, and increased expression and activity of the full‐length and the splice variants of androgen receptor (AR) have been indicated to drive castration resistance. Consequently, there is an urgent need to develop agents that can target both the full‐length and the splice variants of AR for more effective treatment of prostate cancer. In the present study, we showed that raddeanin A (RA), an oleanane‐type triterpenoid saponin, suppresses the transcriptional activities of both the full‐length and the splice variants of AR. This is attributable to their decreased expression as a result of RA induction of proteasome‐mediated degradation and inhibition of the transcription of the AR gene. We further showed the potential of using RA to enhance the growth inhibitory efficacy of docetaxel, the first‐line chemotherapy for prostate cancer. This study identifies RA as a new agent to target both the full‐length and the splice variants of AR and provides a rationale for further developing RA for prostate cancer treatment.

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Section: Discussionsupporting

confidence: 84%

mentioning

confidence: 99%

Raddeanin A down‐regulates androgen receptor and its splice variants in prostate cancer

Xia

Bai

et al. 2019

J Cellular Molecular Medi

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“…The pathway analysis showed significant enrichment in prolactin signaling, RA biosynthesis signaling, PIWI-interacting RNA (piRNA) biogenesis, and IL-2 signaling, among others. These GO terms and pathways are all crucial for the development and progression of cancer [35–37]. Further studies are required, and our prediction of these functional mechanisms may provide a foundation for future research.…”

Section: Discussionmentioning

confidence: 99%

A Simple Competing Endogenous RNA Network Identifies Novel mRNA, miRNA, and lncRNA Markers in Human Cholangiocarcinoma

Zhang

2019

BioMed Research International

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Background. Cholangiocarcinoma (CCA) is the second most common malignant primary liver tumor and has shown an alarming increase in incidence over the last two decades. However, the mechanisms behind tumorigenesis and progression remain insufficient. The present study aimed to uncover the underlying regulatory mechanism on CCA and find novel biomarkers for the disease prognosis. Method. The RNA-sequencing (RNA-seq) datasets of lncRNAs, miRNAs, and mRNAs in CCA as well as relevant clinical information were obtained from the Cancer Genome Atlas (TCGA) database. After pretreatment, differentially expressed RNAs (DERNAs) were identified and further interrogated for their correlations with clinical information. Prognostic RNAs were selected using univariate Cox regression. Then, a ceRNA network was constructed based on these RNAs. Results. We identified a total of five prognostic DEmiRNAs, 63 DElncRNAs, and 90 DEmRNAs between CCA and matched normal tissues. Integrating the relationship between the different types of RNAs, an lncRNA-miRNA-mRNA network was established and included 28 molecules and 47 interactions. Screened prognostic RNAs involved in the ceRNA network included 3 miRNAs (hsa-mir-1295b, hsa-mir-33b, and hsa-mir-6715a), 7 lncRNAs (ENSG00000271133, ENSG00000233834, ENSG00000276791, ENSG00000241155, COL18A1-AS1, ENSG00000274737, and ENSG00000235052), and 18 mRNAs (ANO9, FUT4, MLLT3, ABCA3, FSCN2, GRID2IP, NCK2, MACC1, SLC35E4, ST14, SH2D3A, MOB3B, ACTL10, RAB36, ATP1B3, MST1R, SEMA6A, and SEL1L3). Conclusions. Our study identified novel prognostic makers and predicted a previously unknown ceRNA regulatory network in CCA and may provide novel insight into a further understanding of lncRNA-mediated ceRNA regulatory mechanisms in CCA.

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“…Yu and co-workers discovered the anti-proliferative and apoptotic effects of RA in colorectal LOVO and SW480 cell lines [103]. The study was further extended to in vivo xenograft mouse model, where RA had significantly inhibited the tumor growth through modulation of Wnt/β-catenin signaling via downregulation of p-LRP6, upregulation of AKT inactivation, inhibition of β-catenin and removal of GSK-3β inhibition.…”

Section: Colorectal Cancermentioning

confidence: 96%

Anticancer Potential of Raddeanin A, a Natural Triterpenoid Isolated from Anemone raddeana Regel

et al. 2020

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Natural compounds extracted from plants have gained immense importance in the fight against cancer cells due to their lesser toxicity and potential therapeutic effects. Raddeanin A (RA), an oleanane type triterpenoid is a major compound isolated from Anemone raddeana Regel. As an anticancer agent, RA induces apoptosis, cell cycle arrest, inhibits invasion, migration and angiogenesis in malignant cell lines as well as in preclinical models. In this systemic review, the pharmacological effects of RA and its underlying molecular mechanisms were carefully analyzed and potential molecular targets have been highlighted. The apoptotic potential of RA can be mediated through the modulation of Bcl-2, Bax, caspase-3, caspase-8, caspase-9, cytochrome c and poly-ADP ribose polymerase (PARP) cleavage. PI3K/Akt signaling pathway serves as the major molecular target affected by RA. Furthermore, RA can block cell proliferation through inhibition of canonical Wnt/β-catenin signaling pathway in colorectal cancer cells. RA can also alter the activation of NF-κB and STAT3 signaling pathways to suppress invasion and metastasis. RA has also exhibited promising anticancer potential against drug resistant cancer cells and can enhance the anticancer effects of several chemotherapeutic agents. Overall, RA may function as a promising compound in combating cancer, although further in-depth study is required under clinical settings to validate its efficacy in cancer patients.

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Raddeanin A inhibits growth and induces apoptosis in human colorectal cancer through downregulating the Wnt/β-catenin and NF-κB signaling pathway

Cited by 27 publications

References 55 publications

Raddeanin A down‐regulates androgen receptor and its splice variants in prostate cancer

Raddeanin A down‐regulates androgen receptor and its splice variants in prostate cancer

A Simple Competing Endogenous RNA Network Identifies Novel mRNA, miRNA, and lncRNA Markers in Human Cholangiocarcinoma

Anticancer Potential of Raddeanin A, a Natural Triterpenoid Isolated from Anemone raddeana Regel

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