Effects of fucoidan on proliferation, AMP-activated protein kinase, and downstream metabolism- and cell cycle-associated molecules in poorly differentiated human hepatoma HLF cells

Kawaguchi, Takumi; Hayakawa, Masako; Koga, Hironori; Torimura, Takuji

doi:10.3892/ijo.2015.2928

Cited by 20 publications

(20 citation statements)

References 39 publications

(50 reference statements)

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“…The results of the present study demonstrated that the protein level of p27 was increased in CMTM7‐overexpressed cells, which led to the further inhibition of cell cycle progression. In addition, AMP‐activated protein kinase (AMPK) has also been reported to be involved in the cell growth of liver cancer cells via regulation of cyclin D1, CDK4, and CDK6 . However, whether CMTM7 regulates AMPK was not examined in the present study, and these experiments will be performed in our future work.…”

Section: Discussionmentioning

confidence: 91%

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Overexpression of CMTM7 inhibits cell growth and migration in liver cancer

Huang

Yang

et al. 2019

The Kaohsiung J of Med Scie

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Chemokine‐like factor (CKLF)‐like, MAL and related proteins for vesicle trafficking and membrane link (MARVEL) transmembrane domain‐containing family proteins (CMTMs) have significant roles in the immune system, in male reproduction, as well as in tumorigenesis. Previous studies have shown that CMTM family member 7 (CMTM7) was broadly expressed in various normal tissues, but not in lung, gastric, esophageal, pancreas, and cervix cancers. To explore its relationship with liver cancer, we examined the expression of CMTM7 in liver cancers and its correlation with clinical and pathological conditions. We found that CMTM7 expression was markedly reduced in liver cancer tissues, and negatively correlated with TNM staging and tumor metastasis. In vitro studies showed that enforced expression of CMTM7 inhibited the cell growth and migration of liver cancer cells. Further analysis revealed that CMTM7 suppressed AKT signaling and induced cell cycle arrest at the G0/G1 phase in the liver cancer cells, likely as the consequent of decreased levels of cyclin D1, cyclin‐dependent kinase 4 (CDK4), and CDK6, and increased p27 expression. Thus, CMTM7 functions as a tumor suppressor in liver cancer through suppressing cell cycle progression.

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Section: Discussionmentioning

confidence: 91%

“…In addition, AMP-activated protein kinase (AMPK) has also been reported to be involved in the cell growth of liver cancer cells via regulation of cyclin D1, CDK4, and CDK6. 28 However, whether CMTM7 regulates AMPK was not examined in the present study, and these experiments will be performed in our future work.…”

Section: Discussionmentioning

confidence: 94%

Overexpression of CMTM7 inhibits cell growth and migration in liver cancer

Huang

Yang

et al. 2019

The Kaohsiung J of Med Scie

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“…24 Fucoidan significantly blocks the proliferation of human hepatoma HLF cells, a poorly differentiated HCC cell line, and maintains the cell cycle in the G1/S phase. 2 Hence, the hypothesis of the present study is that fucoidan can induce apoptosis and inhibit the proliferation of HCC cells via modulation of the p38 MAPK/ERK and PI3K/Akt pathways. Here, a mouse xenograft tumor model was used to assess the potential of fucoidan as an adjuvant therapeutic agent against HCC.…”

Section: Introductionmentioning

confidence: 86%

“…Fucoidan is a fucose-rich sulfated carbohydrate derived from brown seaweed, that possesses anti-oxidant, anti-viral, anti-angiogenic, anti-inflammatory, antiproliferative, and anti-bacterial properties as well as anticancer activities against various tumors, especially those of the digestive system. [1][2][3][4][5] The mechanisms underlying the anticancer activities of fucoidan may be related to the targeting of multiple signaling molecules and receptors of various cells, including immune and tumor cells, which could directly induce apoptosis and cytotoxicity of cancer cells. 6 According to recent global cancer statistics, hepatocellular carcinoma (HCC) remains the most common malignancy of the liver.…”

Section: Introductionmentioning

confidence: 99%

<p>Fucoidan Induces Apoptosis and Inhibits Proliferation of Hepatocellular Carcinoma via the p38 MAPK/ERK and PI3K/Akt Signal Pathways</p>

Duan

Xue

et al. 2020

CMAR

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Purpose: Fucoidan is a natural bioactive product with broad therapeutic applications. Hepatocellular carcinoma (HCC) is a common malignancy of the liver associated with a relatively high mortality rate; thus, effective treatments are urgently needed. Here, the effects of fucoidan on HCC and the underlying mechanism were explored. Methods: The proliferation and apoptosis of two HCC cell lines (BEL-7402 and LM3) treated with different concentrations of fucoidan or saline were assessed. The levels of proliferating cell nuclear antigen (PCNA) and CCK8 assay were used to determine proliferative capabilities of BEL-7402 and LM3 cells. Apoptosis of LM3 cells was assessed by Hoechst 33342 staining, Western blotting and flow cytometry. The capability of fucoidan to inhibit the growth of LM3 cells was investigated by monitoring of the p38 MAPK/ERK pathways and the upstream kinases, PI3K/Akt. LM3 xenograft tumors were used for in vivo verification. Results: Cell proliferation and apoptosis assays consistently showed that fucoidan has an inhibitory effect on cell growth. Fucoidan significantly promoted apoptosis of LM3 cells through a mechanism involving activation of caspases 8, 9, and 3 accompanied by changes in B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), as well as changes in the phosphorylation of p38 MAPK and ERK. Fucoidan also altered the phosphorylation of its upstream kinase, Akt. Fucoidan treatment markedly reduced the growth of LM3 xenograft tumors, consistent with the in vitro results. Conclusion: Fucoidan conveys antitumor effects and, thus, should be further explored as a potential treatment option for HCC.

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“…AMP-activated protein kinase (AMPK) is a highly conserved heterotrimeric kinase complex. Activation of AMPK leads to the inhibition of mTORC1 via a tuberous sclerosis complex 2 (TSC2)-dependent or -independent mechanism (6). In animal models with impaired mTORC1 signaling, AMPK is highly activated (7), suggesting a negative crosstalk between these two pathways.…”

Section: Introductionmentioning

confidence: 99%

AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells

Zhan

Wang

et al. 2018

Exp Ther Med

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Age-associated diseases, including vascular diseases, are on the rise with the increase in the aging population. However, the mechanisms of aging and age-associated vascular dysfunction remain to be fully elucidated. Replicative senescence of vascular smooth muscle cells (VSMCs) contributes to aging as well as age-associated vascular diseases. Rapamycin may delay aging-associated diseases via inhibition of the mammalian target of rapamycin (mTOR), but its role in VSMC aging has remained elusive. The present study investigated the involvement of mTOR signaling in replicative senescence of VSMCs. Replicative senescence was induced in human VSMCs by extended passages and identified by assessing the cell morphology, senescence-associated β-galactosidase activity, and p53 and p21 protein expression. Protein expression and phosphorylation were determined by western blot analysis. Significant senescence of VSMCs was observed in cells subjected to extended passaging (until passage 15). Significant decreases in adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2) phosphorylation, but significant increases in mTOR/ribosomal protein S6 kinase 1 (S6K1) phosphorylation, were observed in cells with replicative senescence compared with those in young cells. Pre-treatment of VSMCs with AMPK activator and mTOR inhibitor delayed replicative senescence and reversed changes in AMPKα, TSC2, mTOR and S6K1 phosphorylation in senescent VSMCs. The AMPK/TSC2/mTOR/S6K1 signaling axis was found to have an important role in regulating replicative senescence of human VSMCs.

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Effects of fucoidan on proliferation, AMP-activated protein kinase, and downstream metabolism- and cell cycle-associated molecules in poorly differentiated human hepatoma HLF cells

Cited by 20 publications

References 39 publications

Overexpression of CMTM7 inhibits cell growth and migration in liver cancer

Overexpression of CMTM7 inhibits cell growth and migration in liver cancer

<p>Fucoidan Induces Apoptosis and Inhibits Proliferation of Hepatocellular Carcinoma via the p38 MAPK/ERK and PI3K/Akt Signal Pathways</p>

AMPK/TSC2/mTOR pathway regulates replicative senescence of human vascular smooth muscle cells

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