Lycorine inhibits melanoma cell migration and metastasis mainly through reducing intracellular levels of β‐catenin and matrix metallopeptidase 9

Zhang, Pan; Zhang, Mengli; Yu, Di; Liu, Wenming; Hu, Lin; Zhang, Bin; Zhou, Quansheng; Cao, Zhifei

doi:10.1002/jcp.27732

Cited by 21 publications

(13 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with a recent report that Wnt3a expression is associated with MMP9 expression in primary tumor and metastatic site in recurrent or stage IV colorectal cancer (18). Another study also reported the β-catenin regulation of MMP9 in melanoma using a βcatenin inhibitor lycorine (57). However, in the present study, LiCl was ineffective when the tumoroid grew larger, which mimic later stage of tumors.…”

Section: Discussionsupporting

confidence: 93%

A Reporter System Evaluates Tumorigenesis, Metastasis, β-catenin/MMP Regulation, and Druggability

Sogawa

Eguchi

Okusha

et al. 2019

Tissue Engineering Part A

View full text Add to dashboard Cite

Cancer invasion, metastasis, and therapy resistance are the crucial phenomena in cancer malignancy. The high-expression of matrix metalloproteinase 9 (MMP9) is a biomarker as well as a causal factor of cancer invasiveness and metastatic activity. However, a regulatory mechanism underlying MMP9 expression in cancer is not clarified yet. Additionally, a new strategy for anti-cancer drug discovery is becoming an important clue. In the present study, we aimed (i) to develop a novel reporter system evaluating tumorigenesis, invasiveness, metastasis, and druggability with a combination of three-dimensional (3D) tumoroid model and Mmp9 promoter and (ii) to examine pharmacological actions of anti-cancer medications using this reporter system. High expression and genetic amplification of MMP9 were found in colon cancer cases. We found that proximal promoter sequences of MMP9 in murine and human contained conserved binding sites for transcription factors β-catenin/TCF/LEF, glucocorticoid receptor (GR), and NF-κB. The murine Mmp9 promoter (-569 to +19) was markedly activated in metastatic colon cancer cells and additionally activated by tumoroid formation and by β-catenin signaling stimulator lithium chloride (LiCl). The Mmp9 promoter-driven fluorescent reporter cells enabled the monitoring of activities of MMP9/gelatinase, tumorigenesis, invasion, and metastasis in syngeneic transplantation experiments. We also demonstrated pharmacological actions as follows. ids Dexamethasone and hydrocortisone, steroidal medications binding to GR, inhibited the Mmp9 promoter but did not inhibit tumorigenesis. On the other hand, an antimetabolite 5-fluorouracil, a golden standard for colon cancer chemotherapy, inhibited tumoroid formation but did not inhibit Mmp9 promoter activity. Notably, anti-malaria medication artesunate inhibited both tumorigenesis and the Mmp9 promoter in vitro, potentially through inhibition of βcatenin/TCF/LEF signaling. Thus, this novel reporter system enabled monitoring tumorigenesis, invasiveness, metastasis, key regulatory signalings such as β-catenin/MMP9 axis, and druggability. Impact Statement Cancer invasion and metastasis have been shown to be driven by MMP9, whose expression mechanism is not clarified yet. Additionally, a new strategy for anti-cancer drug discovery is becoming important. We established a novel reporter system evaluating tumorigenesis, invasiveness, metastasis, and druggability with a combination of 3D tumoroid model and Mmp9 promoter. Using this reporter system, we demonstrated pharmacological actions of anti-cancer medications such as an antimetabolite 5fluorouracil and anti-malaria medication artesunate, which inhibited both tumorigenesis and β-catenin/MMP regulatory signaling. Our study impacts the translational fields of oncology, drug discovery, and organoid model. Thus, the specific aims in the present study are (i) to develop a novel reporter system with a combination of 3D tumoroid model for drug discovery, (ii) to investigate whether a novel β-catenin/MMP9 regulatory axis could ...

show abstract

Section: Discussionsupporting

confidence: 93%

A Reporter System Evaluates Tumorigenesis, Metastasis, β-catenin/MMP Regulation, and Druggability

Sogawa

Eguchi

Okusha

et al. 2019

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…Wu et al ( 21 ) have reported that icariin induces apoptosis in human lung adenocarcinoma cells by activating the mitochondrial apoptotic pathway. Furthermore, lycorine has notable antitumor effects in various types of cancer, such as breast, esophageal, ovarian, prostate, melanoma and liver cancer ( 22 ). Acridone alkaloids are another class of natural products primarily obtained from Swinglea glutinosa , which has selective cytotoxicity against human prostate, lung, breast and liver carcinoma cell lines ( 23 ).…”

Section: Natural Products As Antitumor Drugsmentioning

confidence: 99%

Ailanthone: A novel potential drug for treating human cancer (Review)

Ding

Chen

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Cancer is the second leading cause of death after cardiovascular disease. In 2015, >8.7 million people died worldwide due to cancer, and by 2030 this figure is expected to increase to ~13.1 million. Tumor chemotherapy drugs have specific toxicity and side effects, and patients can also develop secondary drug resistance. To prevent and treat cancer, scientists have developed novel drugs with improved antitumor effects and decreased toxicity. Ailanthone (AIL) is a quassinoid extract from the traditional Chinese medicine plant Ailanthus altissima , which is known to have anti-inflammatory and antimalarial effects. An increasing number of studies have focused on AIL due to its antitumor activity. AIL can inhibit cell proliferation and induce apoptosis by up- or downregulating cancer-associated molecules, which ultimately leads to cancer cell death. Antitumor effects of AIL have been observed in melanoma, acute myeloid leukemia, bladder, lung, breast, gastric and prostate cancer and vestibular neurilemmoma. To the best of our knowledge, the present study is the first review to describe the antitumor mechanisms of AIL.

show abstract

“…The ability of cell invasion was detected via transwell assay as we described before 40 . SPC-A-1 and A549 cells in 200 μl of serum-free DMEM were seeded to the upper chamber, and 500 μl of the complete medium was added to the lower chamber.…”

Section: Cell-invasion Assaymentioning

confidence: 99%

“…Proteins from SPC-A-1 and A549 cells were extracted using the MPER Mammalian Protein Extraction Kit, and the western blotting was performed as previously described 40 . After the proteins were resolved by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with Tris-glycine running buffer and transferred to nitrocellulose membranes.…”

Section: Western Blottingmentioning

confidence: 99%

See 1 more Smart Citation

Correction of the tumor suppressor Salvador homolog-1 deficiency in tumors by lycorine as a new strategy in lung cancer therapy

Zhao

Xiang

et al. 2020

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Salvador homolog-1 (SAV1) is a tumor suppressor required for activation of the tumor-suppressive Hippo pathway and inhibition of tumorigenesis. SAV1 is defective in several cancer types. SAV1 deficiency in cells promotes tumorigenesis and cancer metastasis, and is closely associated with poor prognosis for cancer patients. However, investigation of therapeutic strategies to target SAV1 deficiency in cancer is lacking. Here we found that the small molecule lycorine notably increased SAV1 levels in lung cancer cells by inhibiting SAV1 degradation via a ubiquitin-lysosome system, and inducing phosphorylation and activation of the SAV1-interacting protein mammalian Ste20-like 1 (MST1). MST1 activation then caused phosphorylation, ubiquitination, and degradation of the oncogenic Yes-associated protein (YAP), therefore inhibiting YAP-activated transcription of oncogenic genes and tumorigenic AKT and NF-κB signal pathways. Strikingly, treating tumor-bearing xenograft mice with lycorine increased SAV1 levels, and strongly inhibited tumor growth, vasculogenic mimicry, and metastasis. This work indicates that correcting SAV1 deficiency in lung cancer cells is a new strategy for cancer therapy. Our findings provide a new platform for developing novel cancer therapeutics.

show abstract

Lycorine inhibits melanoma cell migration and metastasis mainly through reducing intracellular levels of β‐catenin and matrix metallopeptidase 9

Cited by 21 publications

References 46 publications

A Reporter System Evaluates Tumorigenesis, Metastasis, β-catenin/MMP Regulation, and Druggability

A Reporter System Evaluates Tumorigenesis, Metastasis, β-catenin/MMP Regulation, and Druggability

Ailanthone: A novel potential drug for treating human cancer (Review)

Correction of the tumor suppressor Salvador homolog-1 deficiency in tumors by lycorine as a new strategy in lung cancer therapy

Contact Info

Product

Resources

About