A potent Protein Kinase C modulator isolated from the bryozoan Bugula neritina
Bryostatin 2 is one of a series of cyclic macrolides isolated from the marine bryozoan Bugula neritina (Order Cheilostomata). This arborescent bryozoan is found in temperate and subtropical environments worldwide, but only B. neritina from California and the Gulf of Mexico is known to contain Bryostatins 1, 2, 3, 13 and 15 that are characterized by the C- 20 (E,E)-octa-2-dienoate ester (Pettit et al., 1983)
Bryostatin 2, a macrolide lactone, was first isolated from the bryozoan B. neritina by Pettit et al. (1983) and has recently been postulated to be a product of a bacterial symbiont present in the bryozoan (Davidson et al., 2001).
Schaufelberger et al. (1991) reported a novel scheme for the large-scale isolation of Bryostatin 1 from the bryozoan B. neritina. The reported procedure consists of several organic phase extraction and chromatographic purification steps that can be utilized through slight modifications for the isolation of Bryostatin 2. Subsequently, Bryostatin 2 can be converted to Bryostatin 1 by a selective protection and deprotection strategy of the C-26 hydroxyl group (Pettit, 1991).
Aphios (Castor, 1995, 1997, 1998, 2001) has improved the isolation of Bryostatin 2 from B. neritinautilizing near-critical and supercritical fluids as an alternative to conventional organic solvents techniques, which are time consuming, labor intensive and environmentally insensitive even at a laboratory scale.
Bryostatin 2 is a macrocyclic lactone with anti-tumor properties and a potent activator of Protein Kinase C (PKC), which inhibits the growth of A549 cells (Dale et al., 1989). Bryostatin 2 has been documented to compete with phorbol ester binding to PKC at a Ki= 3.4 nM, a Ki value 1 order magnitude higher than Bryostatin 1, and antagonizes phorbol ester action (Jalava et al., 1990). Bryostatin 2 also exhibits growth inhibitory activity against several human cancer cell lines. It has been shown to inhibit DNA synthesis at 100 nM in SH-SY5Y human neuroblastoma cells (Jalava et al., 1990).
Other studies have shown that Bryostatin 2 can induce arachidonic acid release (Dell'Aquila et al., 1988). Bryostatin 2, along with Bryostatin 1, has been shown to synergistically act with recombinant B cell stimulatory factor-1 to cause differentiation and cytotoxic T lymphocyte development in naïve, resting lymph node T cells (Trenn et al., 1988).
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