A new calyculin derivative from the sponge Theonella swinhoei is a novel and potent inhibitor of tumor cell proliferation.

A novel calyculin derivative was isolated from the marine sponge Theonella swinhoei. Using human and animal tumor cell lines and freshly explanted peripheral blood cells, we investigated several biological effects of this natural product (i.e. cell growth, cytotoxicity, induction of differentiation and apoptosis). The new calyculin exhibited a dose-dependent cytotoxicity against various cell lines from different species and tissues. The ID50 values ranged between 20 and 90 ng/ml. Viability of a multidrug resistant HELA subclone was not affected. Apoptosis of the Hodgkin's lymphoma cell line HDLM-2 induced by antiserum was not prevented by the substance. A reduced drug sensitivity of the monocytic cell line MONOMAC-6 could be observed after induction of differentiation of these cells by phorbol ester and lipopolysaccharide. Even so, non-dividing peripheral blood cells were also resistant to the action of the calyculin derivative, suggesting that the cytotoxin may act preferentially on proliferating cells rather than on quiescent cells. Our data introduce a new calyculin as a marine natural product with interesting features stimulating further studies as a chemotherapeutic or investigational drug.