Fucoidan upregulates TLR4/CHOP-mediated caspase-3 and PARP activation to enhance cisplatin-induced cytotoxicity in human lung cancer cells

Hsu, Hsien Yeh; Lin, Tsai-Yun; Hu, Chun Hao; Shu, David Ta Fu; Lu, Mei-Kuang

doi:10.1016/j.canlet.2018.05.006

Cited by 98 publications

(77 citation statements)

References 27 publications

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“…Tumorigenesis is due to the disruption of the balance between cell proliferation and apoptosis, and apoptosis signal transduction is the key to cell apoptosis. 34 Among them, apoptosis-related proteins such as the caspase 3 protease family 35 , 36 and the anti-apoptotic protein bcl-2 37 , 38 play a key role in apoptosis. By Western blot, 39 , 40 we detected the expression of Cleaved caspase-3 and bcl-2 to verify the apoptosis in tumor cells.…”

Section: Resultsmentioning

confidence: 99%

A study on screening and antitumor effect of CD55-specific ligand peptide in cervical cancer cells

Li¹,

Yin²,

Ji³

et al. 2018

DDDT

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BackgroundTo improve the targeting ability of antitumor drugs, we identified the antigens with high expression on the surface of tumor cells associated with tumor escape, such as the complement regulatory protein CD55 molecule, which is also known as the decay accelerating factor. In this study, phage display technology was used to screen and identify CD55-specific ligand peptide (CD55sp) bound to CD55 molecule on the surface of cervical cancer HeLa cells. We then explored the role of this peptide in inhibiting the growth of cervical cancer cells in vitro. Our characterization of CD55sp will provide implication for tumor target therapy.MethodsThe phage bound to the surface of HeLa cells were isolated by phage display technology. Positive phage clones were identified by ELISA. Phage was then amplified and determined by agarose gel electrophoresis after monoclonal DNA extraction. DNA sequencing and bioinformatical analysis were conducted to obtain specific ligand peptides. Flow cytometry and immunofluorescence were used to measure the expression of CD55 molecule on the surface of tumor and normal cells. Subsequently, the effects of CD55sp on the proliferation and apoptosis of HeLa and SiHa cells were determined by Cell Counting Kit-8 (CCK-8), flow cytometry, and TUNEL assay, respectively. The morphology of apoptotic cells was examined by electron microscope. The distribution of Cleaved caspase-3 was detected by immunofluorescence. The expression of bcl-2 and Cleaved caspase-3 were determined by Western blot.ResultsThe results showed that the peptide (QVNGLGERSQQM) can bind to the CD55 molecule on the surface of cervical cancer HeLa and SiHa cells as a ligand peptide. It can also effectively inhibit the proliferation of cervical cancer cells and induce cell apoptosis.ConclusionThis study demonstrates that CD55sp screened by phage display technology plays a strong antitumor role.

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Section: Resultsmentioning

confidence: 99%

A study on screening and antitumor effect of CD55-specific ligand peptide in cervical cancer cells

Li¹,

Yin²,

Ji³

et al. 2018

DDDT

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“…Moreover, fucoidan induces the death of HCC cells through activation of caspases-7, -8, and -9 [44]. Fucoidan upregulates toll-like receptor 4 (TLR4)/CHOP-mediated caspase-3 and poly (ADP-ribose) polymerase (PARP) stimulation to promote anti-cancer effects of cisplatin in human lung cancer cells [51]. Our results indicate that fucoidan increased cell death via the cleavage of caspase-3 and caspase-9 and the release of cytochrome c in ES-2 and OV-90 cells.…”

Section: Discussionmentioning

confidence: 99%

Fucoidan Derived from Fucus vesiculosus Inhibits the Development of Human Ovarian Cancer via the Disturbance of Calcium Homeostasis, Endoplasmic Reticulum Stress, and Angiogenesis

et al. 2020

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Marine organisms are sources of several natural compounds with potential clinical use. However, only a few marine-based pharmaceuticals have been approved for use due to limited knowledge on their biological activities. Here, we identified the functional role of fucoidan extracted from Fucus vesiculosus on ovarian cancer. Fucoidan increased the death of ES-2 and OV-90 cells, through a reduction in proliferation, cell cycle arrest, releases of cytochrome c, reactive oxygen species (ROS) generation, and endoplasmic reticulum (ER) stress. Additionally, fucoidan increased the concentration of cytosolic and mitochondrial calcium in both cells. The decrease of cell proliferation was controlled by the inactivation of PI3K and MAPK signaling cascades in ES-2 and OV-90 cells. In a toxicity assay with normal zebrafish larvae, fucoidan did not induce toxicity, cardiotoxicity, development, kinesis, and apoptosis at different concentrations. However, it disrupted tumor formation and vascular development in a zebrafish xenograft model and angiogenesis transgenic (Tg, fli1-eGFP) model, respectively. Collectively, the results indicate that fucoidan may be a novel pharmaceutical for the management of human ovarian cancer.

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“…These results confirmed that fucoidan possesses antiproliferation activities mediated by the induction of apoptotic cell death, as reported previously. [31][32][33] The effects of fucoidan are mediated by the PI3K/AKT, ERK, JNK, p38 MAPK, AMPK, GSK and Wnt signaling pathways. 6,34 Specifically, the PI3K/AKT pathway commonly inhibits apoptosis and promotes cell proliferation, while the MAPK pathway modulates cell proliferation, differentiation, apoptosis, and survival.…”

Section: Dovepressmentioning

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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Fucoidan upregulates TLR4/CHOP-mediated caspase-3 and PARP activation to enhance cisplatin-induced cytotoxicity in human lung cancer cells

Cited by 98 publications

References 27 publications

A study on screening and antitumor effect of CD55-specific ligand peptide in cervical cancer cells

A study on screening and antitumor effect of CD55-specific ligand peptide in cervical cancer cells

Fucoidan Derived from Fucus vesiculosus Inhibits the Development of Human Ovarian Cancer via the Disturbance of Calcium Homeostasis, Endoplasmic Reticulum Stress, and Angiogenesis

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

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