Luteolin inhibits proliferation and induces apoptosis of human melanoma cells <i>in vivo</i> and <i>in vitro</i> by suppressing MMP-2 and MMP-9 through the PI3K/AKT pathway

Yao, Xin; Jiang, Wei; Yu, Danhong; Yan, Zhaowei

doi:10.1039/c8fo02013b

Cited by 107 publications

(80 citation statements)

References 32 publications

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“…Luteolin decreased the MMP-2 and MMP-9 expression and increased TIMP-1 and TIMP-2 expression. Inhibition of phosphorylated Akt1 and PI3K suggested that the reduction of MMP-2 and -9 expression was associated with PI3K/AKT pathway [ 61 ].…”

Section: Targeting Metastatic Cancermentioning

confidence: 99%

Flavonoids in Cancer Metastasis

Líšková

Koklesová

Samec

et al. 2020

Cancers

137

128

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Metastasis represents a serious complication in the treatment of cancer. Flavonoids are plant secondary metabolites exerting various health beneficiary effects. The effects of flavonoids against cancer are associated not only with early stages of the cancer process, but also with cancer progression and spread into distant sites. Flavonoids showed potent anti-cancer effects against various cancer models in vitro and in vivo, mediated via regulation of key signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of epithelial-mesenchymal transition or regulatory molecules such as MMPs, uPA/uPAR, TGF-β and other contributors of the complex process of metastatic spread. Moreover, flavonoids modulated also the expression of genes associated with the progression of cancer and improved inflammatory status, a part of the complex process involved in the development of metastasis. Flavonoids also documented clear potential to improve the anti-cancer effectiveness of conventional chemotherapeutic agents. Most importantly, flavonoids represent environmentally-friendly and cost-effective substances; moreover, a wide spectrum of different flavonoids demonstrated safety and minimal side effects during long-termed administration. In addition, the bioavailability of flavonoids can be improved by their conjugation with metal ions or structural modifications by radiation. In conclusion, anti-cancer effects of flavonoids, targeting all phases of carcinogenesis including metastatic progression, should be implemented into clinical cancer research in order to strengthen their potential use in the future targeted prevention and therapy of cancer in high-risk individuals or patients with aggressive cancer disease with metastatic potential.

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Section: Targeting Metastatic Cancermentioning

confidence: 99%

Flavonoids in Cancer Metastasis

Líšková

Koklesová

Samec

et al. 2020

Cancers

137

128

View full text Add to dashboard Cite

show abstract

“…Among these, a reduction of matrix metalloproteinase (MMP)-9 expression, a protein that is involved in extracellular matrix (ECM) degradation, was observed [119]. Moreover, MMP-2 can also be downregulated due to a decrease of phosphorylated AKT, and PI3K proteins [120]. Another target of luteolin is the catalytic subunit of telomerase, hTERT, that is downregulated such as its transcriptional inducer, c-myc, by a mechanism in which the cytoplasmic inactive form of NF-kB is stabilized.…”

Section: Luteolinmentioning

confidence: 99%

Citrus Flavones: An Update on Sources, Biological Functions, and Health Promoting Properties

Barreca

Mandalari

Calderaro

et al. 2020

Plants

103

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Citrus spp. are among the most widespread plants cultivated worldwide and every year millions of tons of fruit, juices, or processed compounds are produced and consumed, representing one of the main sources of nutrients in human diet. Among these, the flavonoids play a key role in providing a wide range of health beneficial effects. Apigenin, diosmetin, luteolin, acacetin, chrysoeriol, and their respective glycosides, that occur in concentrations up to 60 mg/L, are the most common flavones found in Citrus fruits and juices. The unique characteristics of their basic skeleton and the nature and position of the substituents have attracted and stimulated vigorous investigations as a consequence of an enormous biological potential, that manifests itself as (among other properties) antioxidant, anti-inflammatory, antiviral, antimicrobial, and anticancer activities. This review analyzes the biochemical, pharmacological, and biological properties of Citrus flavones, emphasizing their occurrence in Citrus spp. fruits and juices, on their bioavailability, and their ability to modulate signal cascades and key metabolic enzymes both in vitro and in vivo. Electronic databases including PubMed, Scopus, Web of Science, and SciFinder were used to investigate recent published articles on Citrus spp. in terms of components and bioactivity potentials.

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“…Recently, more and more evidence suggests that many Chinese medicinal herbs and their bioactive phytochemicals exhibit potential antitumor functions, providing an alternative therapy strategy for malignant melanoma treatment. For example, increasing studies have confirmed that Luteolin and parthenolide inhibit human melanoma cell proliferation and induce human melanoma cell apoptosis [3,4]. Polyphyllin I, a bioactive constituent extracted from Paris polyphylla, has extensive bioactivities and pharmaceutic activities.…”

Section: Introductionmentioning

confidence: 99%

Polyphyllin I Promoted Melanoma Cells Autophagy and Apoptosis via PI3K/Akt/mTOR Signaling Pathway

Long

2020

BioMed Research International

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To investigate whether Polyphyllin I (PPI) might induce the autophagy and apoptosis of melanoma cells by regulating PI3K/Akt/mTOR signal pathway. Melanoma A375 cells were incubated with different concentrations of Polyphyllin I (0, 1.5, 3.0, and 6.0 mg/L) and PI3K/Akt/mTOR signaling pathway activator IGF-1(20 mg/L). CCK-8 assay was utilized to detect cell proliferation; Cell apoptosis and cell cycle were measured by flow cytometry; Western blot was used to examine the expressions of proteins. Immunofluorescence analysis was performed to evaluate autophagy of A375 cells; In addition, xenograft-bearing nude mice were applied to study the role of Polyphyllin I on melanoma development, melanoma cell proliferation, as well as melanoma cell apoptosis in vivo. The outcomes represented that Polyphyllin I promoted A375 cell apoptosis via upregulating Bax level and cleaved caspase-3 level and downregulating Bcl-2 level, inhibited the growth of A375 cells at the G0/G1 phase, and enhanced cell autophagy via regulating the levels of Beclin 1, LC3II, and p62. However, IGF-1 (an activator of PI3K/Akt/mTOR signal pathway) attenuated these changes that Polyphyllin I induced. Furthermore, the xenograft model experiment confirmed that Polyphyllin I treatment suppressed xenograft tumor growth, increased apoptotic index evaluated by the TUNEL method, and reduced the level of Ki67 in tumor tissues in vivo. In conclusion, Polyphyllin I treatment enhanced melanoma cell autophagy and apoptosis, as well as blocked melanoma cell cycle via suppressing PI3K/Akt/mTOR signal pathway. Meanwhile, Polyphyllin I treatment suppressed the development of melanoma in vivo. Therefore, Polyphyllin I possibly is a promising molecular targeted agent used in melanoma therapy.

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Luteolin inhibits proliferation and induces apoptosis of human melanoma cells in vivo and in vitro by suppressing MMP-2 and MMP-9 through the PI3K/AKT pathway

Abstract: Since the incidence rate of malignant melanoma is increasing annually, development of drugs against melanoma cell metastasis has become more urgent.

Cited by 107 publications

References 32 publications

Flavonoids in Cancer Metastasis

Flavonoids in Cancer Metastasis

Citrus Flavones: An Update on Sources, Biological Functions, and Health Promoting Properties

Polyphyllin I Promoted Melanoma Cells Autophagy and Apoptosis via PI3K/Akt/mTOR Signaling Pathway

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