An effective and inexpensive protocol for producing
cytochalasins A and B is being disclosed to propose a viable method by which to examine the in vivo
antineoplastic activity of these congeners in preclinical
tumor-bearing mammalian models. In addition, we determine the maximum tolerated doses of
cytochalasin B using multiple routes and formulations, characterize the tissue distribution of intravenous bolus
cytochalasin B, and assess the in vivo
antineoplastic activity of
cytochalasin B in comparison in
doxorubicin in Balb/c mice challenged intradermally with M109 murine lung
carcinoma. We also examine the effects of
cytochalasin B against several other murine neoplastic cell lines (Lewis lung, LA4, B16F10, and M5076). Finally, we examine a potential mechanism of the antimetastatic activity of
cytochalasin B by observing the effects of the agent on the secretion of N-
acetylglucosaminidase (GlcNACase) by B16BL6 and B16F10 murine
melanomas in vitro. The results of the study can be summarized as follows: 1)
Cytochalasin B can be safely administered intravenously, intraperitoneally, and subcutaneously in murine models, with the maximum tolerated dose of all routes of administration being increased by
liposome encapsulation. 2)
Cytochalasin B can significantly inhibit the growth of
tumors in mice challenged with M109, Lewis lung, LA4, B16F10, or M5076, producing long-term survival against lung
carcinomas and
adenocarcinomas (M109, Lewis lung, and LA4) and B16F10
melanoma, but not M5076
sarcoma. These effects were comparable to intraperitoneally administered
doxorubicin. 4) Low concentrations of
cytochalasin B inhibit the secretion of GlcNACase, indicating that
cytochalasin B may inhibit metastatic progression by mechanisms not directly associated with its influence on cell adhesion and motility.