Anticancer Activity of the Marine-Derived Compound Bryostatin 1: Preclinical and Clinical Evaluation

Abstract

Bryostatin 1, a natural macrolide isolated from Bugula neritina, is a potent modulator of protein kinase C (PKC) isoforms with promising anticancer properties. In numerous in vitro studies, bryostatin 1 has been shown to inhibit tumor cell proliferation and induce differentiation and apoptotic cell death in a wide range of cell lines, including leukemia, lymphoma, glioma, and solid tumors such as ovarian and breast cancer. Its antitumor activity, both as monotherapy and in combination with conventional chemotherapy, has been confirmed in in vivo models, where synergistic effects have been observed, including sensitization of tumor cells to cytostatic agents. Despite promising preclinical findings, phase I and II clinical trials have not yielded the expected results, suggesting limited efficacy of the macrolide as a single agent with a relatively favorable safety profile. Current research directions focus on optimizing dosing regimens, combining bryostatin 1 with other anticancer drugs and identifying predictive biomarkers of response. This article reviews the current state of knowledge on the anticancer effects of bryostatin 1, analyzing available data from in vitro, in vivo, and clinical trials and discussing potential directions for further translational research.

Keywords: Bryostatin 1; Bugula neritina; anticancer effect; clinical trials; modulator of protein kinase C.

Figure 1

The A-ring and C-ring units described by Keck, Wender and Song as precursors for the synthesis of bryostatin 1. TMS—trimethylsilyl; PMB—para-methoxybenzyl; BOM—benzyloxymethyl; TES—triethylsilyl; TBDPS—tert-butyldiphenylsilyl; TBS—tert-butyldimethylsilyl.

Figure 2

Potential mechanisms of action related to bryostatin 1. Abbreviations: PKC—protein kinase C, SMAC—second mitochondria-derived activator of caspase, DIABLO—direct IAP binding protein with low pI, Omi/HtrA2—proapoptotic mitochondrial serine protease, IAPs—inhibitors of apoptosis proteins, APAF—apoptotic protease activating factor, DISC—death-inducing signaling complex. The red and green arrows indicate increased and decreased expression, respectively.