Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells

Shi, Ming-Der; Liao, Yi-Chen; Shih, Yuan-Wei; Tsai, Li-Yu

doi:10.1016/j.phymed.2013.02.004

Cited by 71 publications

(56 citation statements)

References 33 publications

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“…Besides, the activation of mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) is well known to be associated with tumor invasion and metastasis. Shi et al [117] reported that nobiletin attenuates HGF-induced HepG2 cells metastasis involving both ERK and PI3K/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma. In HT-1080 cells, nobiletin was also evidenced directly inhibited MEK activity and decreases the sequential phosphorylation of ERK, exhibiting the antitumor metastatic activity by suppressing MMP expression [118].…”

Section: Anti-metastasismentioning

confidence: 99%

<i>Citrus</i> Flavonoids and Human Cancers

Ke¹,

Pan²,

Xu³

et al. 2015

JFNR

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Nowadays cancers pose a great threat to the health of human beings. Based on studies on the flavonoids and other bioactive compounds of Citrus fruits in current literature, it was widely suggested that the consumption of Citrus fruits is beneficial to the prevention and treatment of human chronic diseases including cancers. In the past decades, the study concerning Citrus flavonoids has covered various areas including the type, content and distribution of flavonoids in fruits; their variation between wild and cultivated genotypes; their antioxidant, antiinflammation, anti-aging, antimicrobial and anticarcinogenic activities. To enlighten future Citrus germplasm study, this review introduces briefly the functions of main types of Citrus flavonoids, including antioxidant, antiinflammation and anti-aging activities, and their relationships to human cancers. Most importantly, the mechanisms of action by which Citrus flavonoids play their roles in human cancer prevention and treatment were summarized.

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Section: Anti-metastasismentioning

confidence: 99%

<i>Citrus</i> Flavonoids and Human Cancers

Ke¹,

Pan²,

Xu³

et al. 2015

JFNR

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“…Also, it was well documented that activation of matrix metalloproteinase (MMP)-2 and -9 as a proteolytic enzyme in extra cellular matrix (ECM) [10] and urokinase plasminogen activator (uPA) [11, 12] and its receptor (uPAR) [13] is closely involved in metastasis and cancer invasion. In addition, P13K/Akt pathway was known to play a key role in cancer metastasis in cholangiocarcinoma [14], liver cancer [15], colorectal cancer [16], lung cancer [17], esophageal cancer [18] and ovarian cancer [19]. …”

Section: Introductionmentioning

confidence: 99%

“…Recently many medicinal herbs [20, 21] and phytochemicals [15, 22–24] are attractive with anti-metastatic potential with low toxicity. Ocimum sanctum Linne, commonly known as ‘Holy basil’ , [25] was known to have multi-biological effects on immunomodulation, anti-ulcer, anti-inflammation and anti-carcinogenesis [26–29].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of ethanol extract of Ocimum sanctum on osteopontin mediated metastasis of NCI-H460 non-small cell lung cancer cells

Kwak

Sohn

Kim

et al. 2014

BMC Complement Altern Med

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BackgroundOsteopontin (OPN) is one of important molecular targets in cancer progression, metastasis as a calcium-binding, extracellular-matrix-associated protein of the small integrin-binding ligand and, N-linked glycoprotein. In the present study, anti-metastatic mechanism of ethanol extracts of Ocimum sanctum (EEOS) was elucidated on OPN enhanced metastasis in NCI-H460 non- small cell lung cancer cells.MethodsCell viability was measured by MTT assay. Adhesion and invasion assays were carried out to see that EEOS inhibited cell adhesion and invasion in OPN treated and non-treated NCI-H 460 cells. RT-PCR was used to determine the mRNA levels of uPA, uPAR, and EGFR.ResultsEEOS significantly inhibited cell adhesion and invasion in OPN treated and non treated NCI-H460 cells, though EEOS did not show any toxicity up to 200 μg/ml. EEOS effectively attenuated the expression of OPN and CD44 and also OPN activated the expression of CD44 in NCI-H460 cells. In addition, EEOS effectively suppressed the expression of phosphatidylinositide 3-kinases (PI3K) and cyclooxygenase 2 (COX-2) and the phosphorylation of Akt at protein level in OPN treated NCI-H460 cells. Also, EEOS significantly attenuated the expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and epidermal growth factor receptor (EGFR) at mRNA level and reduced vascular endothelial growth factor (VEGF) production and MMP-9 activity in OPN treated NCI-H460 cells. Furthermore, PI3K/Akt inhibitor LY294002 enhanced anti-metastatic potential of EEOS to attenuate the expression of uPA and MMP-9 in OPN treated NCI-H 460 cells.ConclusionOverall, our findings suggest that anti-metastatic mechanism of EEOS is mediated by inhibition of PI3K/Akt in OPN treated NCI-H460 non-small cell lung cancer cells.

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“…Among numerous active flavonoids in citrus fruits, nobiletin has been reported to possess potent biological activities. Previous studies have described various biological effects of nobiletin like anti-inflammatory, anti-tumor, anti-metas -tasis and neuroprotective properties (Murakami et al, 2000;Nakajima et al, 2007;Li et al, 2006;Shi et al, 2013). Recent studies have also demonstrated compelling role of nobiletin in initiating anti-cancerous proper -ties in various cell culture systems (Luo et al, 2009;Ishii et al, 2010).…”

mentioning

confidence: 99%

“…Activation of phosphatidyl inositol 3-kinase (PI3K) leads to phosphorylation of phosphatidyl inositides, which in turn activates the downstream main target, AKT, known to play various imperative roles in regulating cellular growth, adhesion, differentiation and the inflammatory reaction. Nobiletin has been reported to mediate inhibition of tumor promotion through regulation of MAPK/ERK and AKT protein kinase cascades (Shi et al, 2013, Aoki et al, 2013Chen et al, 2014;Lai et al, 2008). Consequently, to elucidate whether nobiletin influences intrinsic apoptotic signaling through ERK or AKT signaling pathway, we performed western blot technique to check the phosphorylation status of ERK and AKT molecules after nobiletin treatment.…”

mentioning

confidence: 99%

Nobiletin acts as a potential anticancer agent against osteosarcoma by regulating ERK and AKT signaling pathways

Fuwen¹,

Zhang²,

Li³

et al. 2014

Bangladesh J Pharmacol

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The current study was aimed to evaluate the anti-proliferative activity of nobiletin, a flavonoid, on osteosarcoma cell line, SaOS-2. Furthermore, we attempted to investigate the signaling pathways involved in the cell growth inhibition mechanism. Upon exposure, nobiletin showed significant cell inhibitory effect on SaOS-2 cells in a dose dependent manner as evidenced by MTT assay and LDH assay. Moreover, flow cytometric analysis demonstrated that upon treatment with nobiletin, SaOS-2 cells underwent apoptosis and showed increased number of cells arrested in G2/M phase. Activation of caspase-9 and -3 indicate the activation of apoptotic signaling pathway in SaOS-2 cells. Additionally, it was observed that the cell inhibitory effect was regulated by the activation of ERK signaling pathway while AKT signaling pathway was down regulated in SaOS-2 cells after 24 h of Nobiletin treatment.

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Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells

Cited by 71 publications

References 33 publications

<i>Citrus</i> Flavonoids and Human Cancers

<i>Citrus</i> Flavonoids and Human Cancers

Inhibitory effect of ethanol extract of Ocimum sanctum on osteopontin mediated metastasis of NCI-H460 non-small cell lung cancer cells

Nobiletin acts as a potential anticancer agent against osteosarcoma by regulating ERK and AKT signaling pathways

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