Activity of dolastatin 10 against small-cell lung cancer in vitro and in vivo: induction of apoptosis and bcl-2 modification

Abstract

These findings suggest that dolastatin 10 has potent activity against SCLC and that the modulation of apoptotic pathways deserves further evaluation as an anticancer strategy.

Phase II trial of dolastatin-10 in patients with advanced breast cancer

“…Dolastatin-10 was found to be a potent inhibitor of tubulin polymerization. It was found to have activity in leukemia, non-Hodgkin's lymphoma, melanoma, lung cancer, prostate, and breast cancer cell models [14][15][16][17][18].…”

“…Pettit [3], dolastatin-10 is a naturally occurring lipophilic linear pentapetide with several unique amino acids. Its mechanism of action includes inhibition of microtubule assembly and induction of apoptosis, possibly through phosphorylation of the bcl-2 protein [4]. It binds to tubulin, inhibiting microtubule assembly, polymerization of purified tubulin, GTPase reaction (tubulin-dependent GTP hydrolysis), and the binding of vinca alkaloids of tubulin.…”

Characterization of apoptosis induced by marine natural products in non small cell lung cancer A549 cells

“…Thus, phosphorylation of serine 136 and 14-3-3 binding serves as a potent inhibitory mechanism to prevent BAD-induced apoptosis. By exerting control over multiple pro-apoptotic proteins, 14-3-3 may function as a general promoter of cell survival [18].…”

“…Its structure is unique in that it contains the sequential positioning of a thiazoline and cyclopropyl ring, and it exerts its potent cell toxicity through interaction with the colchicine drug binding site on microtubules [11][12][13]. Although characterized by distinct structural differences [14], some of these drugs have shown the tendency to trigger apoptosis [15][16][17][18]. In the apoptotic pathway, the Bcl-2 family proteins are well-characterized regulators, consisting of anti-apoptotic and pro-apoptotic members [19,20].…”

Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers

“…alkaloids [6]. Dolastatin-10 is a potent inhibitor of cell growth in a variety of solid tumor cell lines, including gastrointestinal cancer cell lines, as well as in several solid tumor xenograft models [5,[7][8][9]. Myelosuppression was dose-limiting in phase I trials [10][11][12].…”