Anti-Pancreatic Cancer Effects of a Polar Extract From the Edible Sea Cucumber, Cucumaria frondosa

Roginsky, Alexandra B.; Ding, Xianzhong; Woodward, Carl; Ujiki, Michael; Singh, Brahmchetna; Bell, Richard H.; Collin, Peter D.; Adrian, Thomas E.

doi:10.1097/mpa.0b013e3181c72baf

Cited by 32 publications

(25 citation statements)

References 29 publications

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“…It has also been demonstrated that Frondanol A5, an impure extract of Cucumaria frondosa skin from which Frondoside A is originally derived, induced growth inhibition at S and G2-M phase with a decrease in Cdc25c and an increase in p21 WAF1/CIP1 with significant apoptosis associated with H2AX phosphorylation and caspase-2 cleavage in the colon cancer-derived HCT116 cells [4]. A second paper also demonstrated that Frondanol-A5P, a polar precipitate sub-fraction of Frondanol-A5, inhibited proliferation and induced G2/M phase cell cycle arrest in two pancreatic cancer cells with decreased expression of cyclin A, cyclin B, and cdc25c [18]. This anticancer effect of Frondoside A is not tissue specific, and in this context we demonstrated that Frondoside A induced a concentration-dependent decrease in cell viability of the melanoma MDA-MB-435, the breast MCF-7, and the hepatoma HepG2 cells.…”

Section: Discussionmentioning

confidence: 89%

Frondoside A Suppressive Effects on Lung Cancer Survival, Tumor Growth, Angiogenesis, Invasion, and Metastasis

Attoub

Arafat

Gélaude³

et al. 2013

PLoS ONE

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A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition) at 24 h were between 1.7 and 2.5 µM of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days) significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1–0.5 µM) also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer.

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Section: Discussionmentioning

confidence: 89%

Frondoside A Suppressive Effects on Lung Cancer Survival, Tumor Growth, Angiogenesis, Invasion, and Metastasis

Attoub

Arafat

Gélaude³

et al. 2013

PLoS ONE

Self Cite

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“…Recently antitumor activities have been described for crude fractions and isolated single glycosides from sea cucumbers [2-5]. Frondoside A, a triterpenoid glycoside isolated from the sea cucumber Cucumaria frondosa inhibited proliferation and induced apoptosis of pancreatic cancer cell lines as well as growth of human pancreatic and breast cancer xenografts [2,3,5]. A parent compound, Frondanol A5, also inhibited growth of a human colon cancer cell line and, furthermore, prevented primary colon carcinogenesis in a rat model [4].…”

Section: Introductionmentioning

confidence: 99%

Frondoside A inhibits breast cancer metastasis and antagonizes prostaglandin E receptors EP4 and EP2

Kundu

Collin

et al. 2011

Breast Cancer Res Treat

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Frondoside A, derived from the sea cucumber Cucumaria frondosa has demonstrable anticancer activity in several models, however, the ability of Frondoside A to affect tumor metastasis has not been reported. Using a syngeneic murine model of metastatic breast cancer, we now show that Frondoside A has potent antimetastatic activity. Frondoside A given i.p. to mice bearing mammary gland implanted mammary tumors, inhibits spontaneous tumor metastasis to the lungs. The elevated Cyclooxygenase -2 activity in many malignancies promotes tumor growth and metastasis by producing high levels of PGE2 which acts on the prostaglandin E receptors, chiefly EP4 and EP2. We examined the ability of Frondoside A to modulate the functions of these EP receptors. We now show that Frondoside A antagonizes the prostaglandin E receptors EP2 and EP4. 3H-PGE2 binding to recombinant EP2 or EP4-expressing cells was inhibited by Frondoside A at low μM concentrations. Likewise, EP4 or EP2-linked activation of intracellular cAMP as well as EP4-mediated ERK1/2 activation were also inhibited by Frondoside A. Consistent with the antimetastatic activity observed in vivo, migration of tumor cells in vitro in response to EP4 or EP2 agonists was also inhibited by Frondoside A. These studies identify a new function for an agent with known antitumor activity, and show that the antimetastatic activity may be due in part to a novel mechanism of action. These studies add to the growing body of evidence that Frondoside A may be a promising new agent with potential to treat cancer and may also represent a potential new modality to antagonize EP4.

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“…The antitumor activity of frondoside A and cucumariosides is a result of their activity to induce apoptosis of cancer cells (Li et al, 2008; Jin et al, 2009; Roginsky et al, 2010), including HL-60, NB-4, and THP-1 leukemic cells (Jin et al, 2009). …”

Section: Frondoside a And Cucumariosidesmentioning

confidence: 99%

Relationships between chemical structures and functions of triterpene glycosides isolated from sea cucumbers

et al. 2014

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Many marine triterpene glycosides have in vitro and in vivo activities with very low toxicity, suggesting that they are suitable agents for the prevention and treatment of different diseases, particularly cancer. However, the molecular mechanisms of action of natural marine compounds in cancer, immune, and other various cells are not fully known. This review focuses on the structural characteristics of marine triterpene glycosides and how these affect their biological activities and molecular mechanisms. In particular, the membranotropic and membranolytic activities of frondoside A and cucumariosides from sea cucumbers and their ability to induce cytotoxicity and apoptosis have been discussed, with a focus on structure-activity relationships. In addition, the structural characteristics and antitumor effects of stichoposide C and stichoposide D have been reviewed along with underlying their molecular mechanisms.

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Anti-Pancreatic Cancer Effects of a Polar Extract From the Edible Sea Cucumber, Cucumaria frondosa

Cited by 32 publications

References 29 publications

Frondoside A Suppressive Effects on Lung Cancer Survival, Tumor Growth, Angiogenesis, Invasion, and Metastasis

Frondoside A Suppressive Effects on Lung Cancer Survival, Tumor Growth, Angiogenesis, Invasion, and Metastasis

Frondoside A inhibits breast cancer metastasis and antagonizes prostaglandin E receptors EP4 and EP2

Relationships between chemical structures and functions of triterpene glycosides isolated from sea cucumbers

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