Hunting (Edible) Starfishes for PAK1-blocking Saponins

Recently several anti-cancer saponins were isolated from marine organisms such as “edible” sea cucumbers and starfishes. One of these marine saponins is Frondoside A from sea cucumber (Cucumaria frondosa) which suppresses the growth of pancreatic cancer in vivo (xenograft in mice). Since the growth of pancreatic cancers depends on PAK1, and this saponin induces p21, a CDK-inhibiting protein, whose gene is activated by PAK1-blockers, it is most likely that Frondoside A (FRA) is a PAK1-blocker. Recently we confirmed that FRA indeed inhibits PAK1 directly.

More recently a Korean group found another anti-cancer saponin in methanol extract from an edible starfish grown in Vietnam coast line (1).  The IC₅₀ of this extract against cancer cells is around 1 ppm (1 micro g/ml). In other words, its anti-PAK index is around 100, several times more potent than Bio 30, a CAPE-based propolis. Furthermore, it inactivates the oncogenic kinase ERK, just downstream of PAK1. Thus, we recently started hunting starfishes along Okinawa coast line, screening for a similarly (or even more) potent anti-cancer (PAK1-blocking) saponin(s).

References:

1. Thao NP, Luyen BT, Kim EJ, Kang HK, Kim S, Cuong NX, Nam NH, Kiem PV, Minh CV, Kim YH. 　Asterosaponins from the Starfish Astropecten monacanthus suppress growth and induce apoptosis in HL-60, PC-3, and SNU-C5 human cancer cell lines. Biol Pharm Bull. 2014;　37(2):　315-21.