Caspase-dependent and caspase-independent induction of apoptosis in breast cancer by fucoidan via the PI3K/AKT/GSK3β pathway in vivo and in vitro

Xue, Meilan; Ji, Xinqiang; Xue, Chuanxing; Liang, Hui; Ge, Yubin; He, Xueling; Zhang, Li; Bian, Kang; Zhang, Lichen

doi:10.1016/j.biopha.2017.08.013

Cited by 68 publications

(60 citation statements)

References 31 publications

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“…Treatment with 820 μg/mL of low molecular weight (LMW) fucoidan resulted in a significant decrease in anti-apoptotic proteins Bcl-2, Bcl-xl and Mcl-1 in MDA-MB231 breast cancer cells [35]. Similarly, Xue et al also demonstrated that fucoidan treatment downregulated the expression of Bid, Bcl-2 and Bcl-xl and up-regulated the level of Bax, especially at 25 μg/ml in MDA-MB231 breast cancer cells [47]. Our study had similar results, where fucoidan induced apoptosis via up-regulation of the Bax/Bcl-2 ratio in ELT-3 cells.…”

Section: Discussionmentioning

confidence: 87%

“…In our study, we found that fucoidan treatment decreased the levels of β-catenin in both the cytoplasm and the nucleus in ELT-3 cells and abolished the TGFβ3-induced β-catenin translocation into the nucleus. Similarly, Xue et al demonstrated that fucoidan treatment decreased the levels of β-catenin in the cytoplasm and nucleus of MDA-MB-231 cells [47].…”

Section: Discussionmentioning

confidence: 99%

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Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

Chen

Huang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Uterine leiomyomas (ULs) are benign uterine tumors, and the most notable pathophysiologic feature of ULs is excessive accumulation of extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown seaweeds that has a wide range of pharmacological properties, including anti-fibrotic effects. We aimed to study the effect of fucoidan on the growth of ULs activated by transforming growth factor beta (TGFβ). Methods: We used ELT-3 (Eker rat leiomyoma tumor-derived cells) and HUtSMC (human uterine smooth muscle cells) as in vitro models. Cell viability was determined by the MTT assay. Cell colony formation was stained using crystal violet. The side population, cell cycle and apoptosis were analyzed using flow cytometry. Protein expression was assayed by western blot analysis. We also conducted in vivo experiments to confirm the inhibitory effects of fucoidan in nude mouse xenograft models. Tumor tissues were assayed by immunohistochemistry analysis. Results: In our study, fucoidan caused a 50% growth inhibition using a dose of 0.5 mg/ml and decreased the stem cell activity after 48 h. In addition, fucoidan induced sub-G1 cell cycle arrest and apoptosis. Fucoidan down-regulated fibronectin, vimentin, α-SMA and the COL1A1 protein levels in TGFβ3-induced ELT-3 cells. In the cellular mechanism, fucoidan abrogated TGFβ3-induced levels of p-Smad2 and p-ERK1/2, as well as β-catenin translocation into the nucleus. Furthermore, fucoidan suppressed xenograft tumor growth in vivo. Conclusion: Fucoidan displays anti-proliferation and anti-fibrotic effects and exerts protective effects against ULs development.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

Chen

Huang

et al. 2018

Cell Physiol Biochem

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“…Pro-apoptotic activity of fucoidan was previously reported in i.a. colon carcinoma and breast cancer cells (Chen et al 2014; Hyun et al 2009; Xue et al 2017). Our results confirmed such observations among uterine sarcomas cell lines, furthermore we noted that it influence cell cycle by arresting it in G0/G1 (not dividing cells) and sub-G1 (apoptotic cells).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Fucoidan, a Potential New, Natural, Anti-Neoplastic Agent on Uterine Sarcomas and Carcinosarcoma Cell Lines: ENITEC Collaborative Study

Bobinski

Okła

Bednarek

et al. 2019

Arch. Immunol. Ther. Exp.

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The aim of the study was to assess the activity of fucoidan on the uterine sarcomas (MES-SA and ESS-1) and carcinosarcoma cell lines (SK-UT-1 and SK-UT-1B) and its toxicity on the human skin fibroblasts (HSF). Two uterine sarcomas and two carcinosarcoma cell lines were examined, as a control HSF were used. Cell viability was assessed with MTT test, apoptosis with caspase-3 activity and cell cycle by assessment of DNA synthesis. Fucoidan significantly decreases cell viability in SK-UT-1, SK-UT-1B, and ESS-1 cell lines, such effect was not observed in MES-SA. Fucoidan was not substantially affecting proliferation among normal cells. The tested agent induced apoptosis in all cell cultures used in the experiment. Fucoidan affects cell cycle of all tested cell lines except MES-SA by increasing percentage of cells in G0/sub-G1/G1 phase. Fucoidan do not only affect proliferation but induces apoptosis in selected uterine sarcoma and carcinosarcoma cell lines, so it has potential to be used as cytotoxic agent. Fucoidan seems to be promising anti-cancer agent for endometrial stromal sarcoma and carcinosarcoma.Electronic supplementary materialThe online version of this article (10.1007/s00005-019-00534-9) contains supplementary material, which is available to authorized users.

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“…Álvarez-viñas et al [15] recently compared <5, 5-10, 10-30, 30-50, 50-100 and >100 kDa of fucoidan extracts from S. muticum for their anti-cancer activity against cervical cancer (HeLa 229), ovarian cancer (A2780), hepatocarcinoma (HepG2) and kidney (LLC-PK1) cells. The results showed that overall, HeLa 229 and A2780 cells were more strongly inhibited than HepG2 and LLC-PK1 cells, and even though the maximal sulphate content was found in the >100 kDa fraction, the cytotoxic activity was maximal for the 5-30 kDa fraction.Anti-tumor or anti-cancer activities of different fucoidans havebeen widely investigated for breast cancer [7,[21][22][23][24], colon/colorectal cancer [3,[25][26][27][28], liver cancer [13,29], lymphoma [8] and lung cancer [11,30]. However, the effect of fucoidan on osteosarcoma has only recently been investigated [31][32][33].Osteosarcoma is the most common type of bone cancer occurring in the proximal humerus (usually around the knee), distal femur and proximal tibia of younger children (more than 5 years of age), teenagers (it is the third most common cancer in adolescence) and older adults [34].…”

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confidence: 99%

Fucoidan Inhibition of Osteosarcoma Cells is Species and Molecular Weight Dependent

et al. 2020

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Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anti-cancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10–50 kDa), medium (MMW, 50–100 kDa) and high (HMW, >100 kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had the highest levels of sugars, acids and sulphation among molecular weight fractions. There was a dose-dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in the sub-G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress-induced apoptosis-like cell death for F. vesiculosus fucoidan and features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.

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Caspase-dependent and caspase-independent induction of apoptosis in breast cancer by fucoidan via the PI3K/AKT/GSK3β pathway in vivo and in vitro

Cited by 68 publications

References 31 publications

Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

The Effect of Fucoidan, a Potential New, Natural, Anti-Neoplastic Agent on Uterine Sarcomas and Carcinosarcoma Cell Lines: ENITEC Collaborative Study

Fucoidan Inhibition of Osteosarcoma Cells is Species and Molecular Weight Dependent

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