Frondoside A enhances the antiproliferative effects of gemcitabine in pancreatic cancer

Shemaili, J. Al; Mensah-Brown, Eric; Parekh, K.; Thomas, S.A.; Attoub, Samir; Hellman, Björn; Nyberg, Frida; Adem, Abdu; Collin, Peter D.; Adrian, Thomas E.

doi:10.1016/j.ejca.2014.01.002

Cited by 37 publications

(36 citation statements)

References 12 publications

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“…Sea cucumber is a kind of nutritious echinoderm. It has been proven to have antioxidant, antibacterial, and antitumor effects . It contains a variety of active molecules, including holothurin A (HA), philinopside A, philinopside E, stichoposide C, stichoposide D, frondoside A, ds‐echinoside A, 24‐dehydroechinoside A (DHEA), cucumarioside А2–2, and so forth .…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that these molecules can inhibit tumor progression through many different mechanisms. For example, frondoside A, isolated from Cucumaria frondosa , can inhibit the proliferation of pancreatic cancer, lung cancer, and breast cancer cell lines and increase the expression of the p53 and p21 genes and promote apoptosis via the cas3/7 pathway . It also inhibits cell migration and invasion of breast cancer by inhibiting the prostaglandin receptor EP2/EP4 and blocking extracellular signal‐regulated kinase 1/2 (ERK1/2) activation .…”

Section: Introductionmentioning

confidence: 99%

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Sea cucumber extract TBL‐12 inhibits the proliferation, migration, and invasion of human prostate cancer cells through the p38 mitogen‐activated protein kinase and intrinsic caspase apoptosis pathway

et al. 2019

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Background: Sea cucumber is a kind of nutritious echinoderm that has multiple biological activities, including antioxidant, antibacterial, and antitumor activities.However, there is no extensive study on the antitumor effect of sea cucumber extract on prostate cancer (PCa). TBL-12 is a new sea cucumber extract. In this study, we investigated the in vivo anti-PCa effect of TBL-12 and its in vitro effects on the proliferation, apoptosis, migration, and invasion of the human PCa cell lines LNCaP, 22RV1, PC-3, and DU145, and evaluated its possible mechanisms. Methods: Cell proliferation was analyzed by cell counting kit-8 and colony formation assays. Scratch migration assay and transwell invasiveness assay were used to observe TBL-12 effect on the migration and invasion of PCa cells. Matrix metalloproteinase 2 (MMP-2) and MMP-9 expression and enzymatic activity was determined by Western blot analysis, quantitative reverse-transcription polymerase chain reaction, and gelatin zymography. Apoptosis level was detected by flow cytometry analysis. Western blot analysis was used to analyze p38 mitogen-activated protein kinase (MAPK) and apoptosis pathways. Angiogenic array analysis was used to explore autocrine and paracrine growth factors in PCa cell lines. Xenograft tumor model was built to observe the in vivo anticancer effect. Results: TBL-12 could significantly inhibit tumor growth in xenograft PCa mice in vivo, and dramatically inhibit the proliferation, colony formation, migration, and invasiveness of PCa cells in vitro (P < 0.05 and P < 0.001). The expression and enzyme activity of MMP-2 and MMP-9 were significantly suppressed by TBL-12 (P < 0.01), and decreased phosphorylation level of p38 in PCa cells was detected (P < 0.001). Furthermore, TBL-12 could reinforce the MMP-2/MMP-9 inhibitory effect of SB203580, a specific inhibitor of the p38 MAPK pathway (P < 0.05). Besides, TBL-12 could induce the apoptosis of PCa cells by activating caspase-9, caspase-7, and poly(ADP-ribose) polymerase and suppressing survivin, and inhibit The Prostate. 2019;79:826-839. wileyonlinelibrary.com/journal/pros 826 | 1 Yuan and Huang contributed equally to this study. the secretion of angiogenin, angiopoietin-2, and vascular endothelial growth factor in PCa cells. Conclusions: Sea cucumber extract TBL-12 could suppress the proliferation and metastasis of human PCa cells by inhibiting MMP-2 and MMP-9 via blocking the p38 MAPK pathway, inducing apoptosis through intrinsic caspase apoptosis pathway and inhibiting the secretion of angiogenic factors. Our findings may be of importance and significance for the research and clinical applications of sea cucumber extract in PCa treatment. K E Y W O R D S apoptosis, matrix metalloproteinases, prostate cancer, sea cucumber extract, tumor metastasis SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Yuan L, Huang X, Zhou K, et al. Sea cucumber extract TBL-12 inhibits the proliferatio...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sea cucumber extract TBL‐12 inhibits the proliferation, migration, and invasion of human prostate cancer cells through the p38 mitogen‐activated protein kinase and intrinsic caspase apoptosis pathway

et al. 2019

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“…Since these tumors are resistant to gem therapy (16–18), in the L3.6pl PDAC model, increasing gem transport would not improve the therapeutic efficacy, thus isolating the effect of nAb-PTX transport component in the combination therapy. As opposed to L3.6pl PDAC model, other human PDAC mouse models are sensitive to gem treatment and, therefore, they could not be implemented in our experiments (19–21). Additionally, we have previously shown that this orthotopic model of slow developing PDAC that takes at least 30 days to develop, can produce a dense stroma comparable to the tumor microenvironment in the clinical PDAC specimens (16).…”

Section: Introductionmentioning

confidence: 99%

Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma

et al. 2017

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The mechanism for improved therapeutic efficacy of the combination therapy with albumin-bound paclitaxel (nAb-PTX) and gemcitabine (gem) for pancreatic ductal adenocarcinoma (PDAC) has been ascribed to enhanced gem transport by nAb-PTX. Here, we used an orthotopic mouse model of gem-resistant human PDAC in which increasing gem transport would not improve the efficacy, thus revealing the importance of nAb-PTX transport. We aimed to evaluate therapeutic outcomes and transport of nAb-PTX to PDAC as a result of: (1)encapsulating nAb-PTX in multistage nanovectors (MSV); (2)effect of gem on caveolin-1 expression. Treatment with MSV/nAb-PTX+gem was highly efficient in prolonging animal survival in comparison to other therapeutic regimens. MSV/nAb-PTX+gem also caused a substantial increase in tumor PTX accumulation and significantly reduced tumor growth and tumor cell proliferation, and increased apoptosis. Moreover, gem enhanced caveolin-1 expression in vitro and in vivo, thereby improving transport of nAb-PTX to PDAC. This data was confirmed by analysis of PDACs from patients who received gem-based neo-adjuvant chemotherapy. In conclusion, we found that nAb-PTX treatment of gem-resistant PDAC can be enhanced by: (1)gem through up-regulation of caveolin-1; (2)MSV through increasing accumulation of nAb-PTX in the tumor.

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“…Frondoside A, a triterpenoid, was originally isolated from an extract of the Atlantic sea cucumber Cucumaria frondosa, and cannot chemically be synthesized due to its complex structure [11,12] (Figure 1A). Several studies have reported that frondoside A exerts an antiproliferative and pro-apoptotic activity [13][14][15][16]. Moreover, this compound is capable of potentiating the anticancer effects of conventional cytotoxic drugs such as gemcitabine and 5-fluorouracil [13,16].…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have reported that frondoside A exerts an antiproliferative and pro-apoptotic activity [13][14][15][16]. Moreover, this compound is capable of potentiating the anticancer effects of conventional cytotoxic drugs such as gemcitabine and 5-fluorouracil [13,16]. Detailed molecular analyses revealed that these effects are mainly mediated by the inhibition of PI3K, resulting in reduced Akt signaling and caspase-induced cell death [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation

et al. 2020

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Background:The marine-derived triterpenoid frondoside A inhibits the phosphatidylinositol-3-kinase (PI3K) pathway in cancer cells. Because this pathway is also crucially involved in platelet activation, we studied the effect of frondoside A on thrombus formation. Methods: Frondoside A effects on platelet viability, surface adhesion molecule expression, and intracellular signaling were analyzed by flow cytometry and Western blot. The effect of frondoside A was analyzed by photochemically induced thrombus formation in the mouse dorsal skinfold chamber model and by tail vein bleeding. Results: Concentrations of up to 15 µM frondoside A did not affect the viability of platelets, but reduced their surface expression of P-selectin (CD62P) and the activation of glycoprotein (GP)IIb/IIIa after agonist stimulation. Additional mechanistic analyses revealed that this was mediated by downregulation of PI3K-dependent Akt and extracellular-stimuli-responsive kinase (ERK) phosphorylation. Frondoside A significantly prolonged the complete vessel occlusion time in the mouse dorsal skinfold chamber model of photochemically induced thrombus formation and also the tail vein bleeding time when compared to vehicle-treated controls. Conclusion: Our findings demonstrated that frondoside A inhibits agonist-induced CD62P expression and activation of GPIIb/IIIa. Moreover, frondoside A suppresses thrombus formation. Therefore, this marine-derived triterpenoid may serve as a lead compound for the development of novel antithrombotic drugs.

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Frondoside A enhances the antiproliferative effects of gemcitabine in pancreatic cancer

Cited by 37 publications

References 12 publications

Sea cucumber extract TBL‐12 inhibits the proliferation, migration, and invasion of human prostate cancer cells through the p38 mitogen‐activated protein kinase and intrinsic caspase apoptosis pathway

Sea cucumber extract TBL‐12 inhibits the proliferation, migration, and invasion of human prostate cancer cells through the p38 mitogen‐activated protein kinase and intrinsic caspase apoptosis pathway

Gemcitabine enhances the transport of nanovector-albumin-bound paclitaxel in gemcitabine-resistant pancreatic ductal adenocarcinoma

The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation

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