Lycorine possesses notable anticancer potentials in on-small cell lung carcinoma cells via blocking Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT)

Sun, Yanfang; Wu, Pingping; Sun, Yang; Sharopov, Farukh; Yang, Qun; Chen, Fang‐Ming; Wang, Pan; Liang, Zongsuo

doi:10.1016/j.bbrc.2017.11.032

Cited by 31 publications

(23 citation statements)

References 23 publications

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“…STAT3 is also suggested a potential target of lycorineinduced anticancer effect as no significant decrease in cell viability was observed in the STAT3 knockdown prostate cancer cell [70]. In nonsmall cell lung cancer, lycorine effectively suppresses the Wnt/β-catenin signaling for EMT reversal [122].…”

Section: Inhibition Of Invasion and Metastasismentioning

confidence: 99%

Lycorine: A prospective natural lead for anticancer drug discovery

Roy

Liang

Xiao

et al. 2018

Biomedicine & Pharmacotherapy

113

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Nature is the most abundant source for novel drug discovery. Lycorine is a natural alkaloid with immense therapeutic potential. Lycorine is active in a very low concentration and with high specificity against a number of cancers both in vivo and in vitro and against various drug-resistant cancer cells. This review summarized the therapeutic effect and the anticancer mechanisms of lycorine. At the same time, we have discussed the pharmacology and comparative structure-activity relationship for the anticancer activity of this compound. The researches outlined in this paper serve as a foundation to explain lycorine as an important lead compound for new generation anticancer drug design and provide the principle for the development of biological strategies to utilize lycorine in the treatment of cancers.

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Section: Inhibition Of Invasion and Metastasismentioning

confidence: 99%

Lycorine: A prospective natural lead for anticancer drug discovery

Roy

Liang

Xiao

et al. 2018

Biomedicine & Pharmacotherapy

113

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“…Although the potential targets and mechanisms of lycorine remain disputable and unclear, its high activity suggests its potential use as an anticancer agent. A previous study showed that lycorine exhibited anti-invasive effects in lung cancer associated with the Wnt/β-catenin pathway [11]. Additionally, lycorine promoted autophagy and induced apoptosis in hepatocellular carcinoma via the TRCP1/Akt/mTOR axis [9].…”

Section: Agingmentioning

confidence: 98%

Lycorine induces autophagy-associated apoptosis by targeting MEK2 and enhances vemurafenib activity in colorectal cancer

Mei

et al. 2020

Aging

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INTRODUCTION Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second most common primary cause of cancer-related mortality worldwide [1]. The burden of global colon cancer is expected to increase to more than 2.2 million new cases and 1.1 million deaths by 2030 [2]. With advancements in medical treatment for CRC in recent decades, therapeutic interventions, including surgical resection, chemotherapy, adjuvant chemotherapy, radiation, and receptor-based targeted therapy, have had favorable effects on the prognosis of CRC [3]. However, recurrence and distant metastasis after surgical resection of CRC remain major complications in treatment [4]. The outcomes of first-line chemotherapeutics such as fluorouracil and oxaliplatin are compromised because of side effects or drug resistance [5]. For stage III CRC,

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“…Second, SAV1 induces the protein kinase-phosphorylation cascade (MST1/2-LAST1/2-YAP/TAZ) in the Hippo pathway and simultaneously inhibits several other tumorigenic signal pathways, such as the AKT and NF-κB signal pathways in cancer cells, therefore amplifying SAV1-mediated tumor suppression. Third, SAV1 overexpression inhibits cancer cell proliferation and motility and induces tumor cell apoptosis 13,61 without obvious side effects in tumorbearing mice. Thus, SAV1 is an excellent target for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Lycorine's anticancer effect is mediated by suppressing expression of numerous oncogenic genes, such β-catenin 40 , m-TOR 70 , Erk 71 , and also by inhibiting multiple signaling pathways, including AKT 72 , Stat3 73 , Wnt-β-catenin 74 , Src-Fak 75 , and NF-κB. Lycorine also blocks EMT and has an anti-colon carcinoma effect 61,76 . In this study, we found that lycorine treatment powerfully activated the tumor-suppressive Hippo pathway, without obvious toxicity in the tumor-bearing mice at the doses tested.…”

Section: Discussionmentioning

confidence: 99%

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

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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.

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Lycorine possesses notable anticancer potentials in on-small cell lung carcinoma cells via blocking Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT)

Cited by 31 publications

References 23 publications

Lycorine: A prospective natural lead for anticancer drug discovery

Lycorine: A prospective natural lead for anticancer drug discovery

Lycorine induces autophagy-associated apoptosis by targeting MEK2 and enhances vemurafenib activity in colorectal cancer

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

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