Deep-Sea Diamond News • November 29, 2019
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 vivoalone and in combination with cisplatin. Frondoside Accused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2over 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 2.5mM 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 (0.1–0.5mM) 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.
Sea cucumbers have been valued for hundreds of years in the theChinese diet as a food delicacy, as well as a medicine for a wide variety of diseases. In the United States and Canada, sea cucumber tissues are dried, pulverized and encapsulated as nutraceuticals for over-the-counter dietary health supplements, primarily directed at inflammatory conditions in humans and companion animals. Frondoside A is a triterpenoid glycoside isolated from the Atlantic cucumber, Cucumaria frondosa. Recent studies demonstrate that low concentrations of Frondoside A inhibit the growth and induced apoptosis of human pancreatic, leukemia and breast cancer cells via caspase activation。
The chemotherapeutic agents currently in use for lung cancer are still unsatisfactory due to associated co-lateral toxicity and drug-induced resistance [9–11] which motivate our investigation of the impact of Frondoside A on human non-small cell lung cancer survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivoalone and in combination with cisplatin.
Frondoside A also impairs lung cancer cell migration and invasion in vitro and metastasis in vivo.
Cancer progression is associated with the abrogation of normal controls that limit cell migration and invasion, eventually, leading to metastasis. Lung cancer patients are at high risk of recurrence in the form of metastatic disease. Metastasis starts with cell migration in the primary tumor, leading to local tissue invasion and entry into lymph or blood vessels. The ability of Frondoside A to reduce cellular migration was investigated using a classic in the vitro wound healing model. Frondoside A reduced cellular migration ofLNM35 cells in a concentration- and time-dependent manner(Fig. 8A). Similarly, Frondoside A impaired the invasion of ofLNM35 cells in Matrigel invasion assay (Fig. 8B). Frondoside A-induced inhibition of cellular migration and matrigel invasion occurred without significant reduction of cell viability.