Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway

Xiao, Ying; Huang, Anling; Xing, Yajing; Lan, Liping; Yi, Zhengfang; He, Ping

doi:10.1007/s11427-016-0368-y

Cited by 64 publications

(52 citation statements)

References 50 publications

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“…Lycorine is extensively studied as an anti-tumour drug and has been demonstrated to have effects on the induction of cell apoptosis [72-77], autophagy [78] and cell cycle arrest [79, 80] in different tumour cell lines. Thus, in the present study, the toxicity of lycorine on endplate cells was carefully assessed, and we found that CEP cells showed no obvious apoptosis or cycle arrest effect at 0.4 µM LY, as this dose is much lower than the anti-tumour effect dose (4-50 µM) used in previous studies.…”

Section: Discussionmentioning

confidence: 99%

Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway

Wang

Huang

Dong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cartilaginous endplate (CEP) degeneration is an important cause for intervertebral disc (IVD) degeneration that leads to low-back pain. The identification of compounds that may prevent CEP degeneration is of interest for the prevention of IVD degeneration. Methods: Catabolic protease expression in the CEP of disc degeneration patients was first assessed. The toxicity, function and underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration were assessed in vitro by flow cytometry analysis and western blotting. The concentration and function of LY in rat-tail disc-degeneration models were also assessed by HPLC (High Performance Liquid Chromatography) quantification and histological analysis. Results: In CEP cells, Interleukin (IL)-1β upregulated the expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 that is critical for the degradation of cartilage extracellular matrix. Interestingly, LY suppressed the expression of these enzymes via the inhibition of nuclear factor-κB (NFκB) signalling and thus prevented IL-1β-induced endplate cell degeneration in vitro. More importantly, LY also reduced the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in CEP and exerted a protective effect on both CEP and nucleus pulposus (NP) degeneration. In addition to its inhibitory effect on matrix-degrading protease expression, LY treatment also reduced positive regulators of proinflammatory cytokines, such as MIF, which can be secreted by CEP cells and subsequently target NP cells. Conclusion: LY could serve as a potential drug for treating IVD disease.

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Section: Discussionmentioning

confidence: 99%

Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway

Wang

Huang

Dong

et al. 2018

Cell Physiol Biochem

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“…Li et al, () found that the combination of lycorine and cytotoxic T‐lymphocyte associated protein 4 antibodies synergistically decreased the lung metastasis of renal cell carcinoma (RCC) in a murine RCC animal model. Ying et al () indicated that lycorine suppressed the proliferation, migration, and invasion in breast cancer cells, and decreased tumor metastasis using a tail vein model of MDA‐MB‐231 cells by suppressing Src/FAK signaling. J. Wang et al () reported the antibreast cancer metastasis function of lycorine in vitro and in vivo through the blockage of STAT3 signaling.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

et al. 2018

Journal Cellular Physiology

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Metastatic melanoma accounts for 60% of death for skin cancer. Although great efforts have been made to treat the disease, effective drugs against metastatic melanoma still lack at the clinical setting. In the current study, we found that lycorine, a small molecule of isoquinoline alkaloid, significantly suppressed melanoma cell migration and invasion in vitro, and decreased the metastasis of melanoma cells to lung tissues in tumor‐bearing mice, resulting in significant prolongation of the survival of the mice without obvious toxicity. Molecular mechanistic studies revealed that lycorine significantly reduced intracellular levels of β‐catenin protein through degradation of the protein via the ubiquitin–proteasome pathway, and decreased the expression of β‐catenin downstream prometastatic matrix metallopeptidase 9 and Axin2 genes. Collectively, our findings support the notion that targeting the oncogenic β‐catenin by lycorine is a new option to inhibit melanoma cell metastasis, providing a good drug candidate potential for development novel therapeutics against metastatic melanoma.

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“…Specificity: The selectivity of lycorine toward cancer cells is an important criterion among them. The concentration that significantly reduces the viability of cancer cells has trivial toxicity against B-lymphocytes [66,67], normal peripheral mononuclear cells, fibroblastic cells [68], normal breast [69], prostate [70], and urothelial cells [71], mammary epithelial cells [72], and even plasma cells from healthy donor [66]. Low concentration: Lycorine is effective in a very low, single-digit micromolar concentration with the reported studies suggesting the IC 50 value usually not exceeded 7.5 μM (Table 1).…”

Section: Anti-tumor Effect Of Lycorinementioning

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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Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway

Cited by 64 publications

References 50 publications

Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway

Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway

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

Lycorine: A prospective natural lead for anticancer drug discovery

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