Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration.

Abstract

Cytochalasin B is a potentially novel microfilament-directed chemotherapeutic agent that prevents actin polymerization, thereby inhibiting cytokinesis. Although cytochalasin B has been extensively studied in vitro, only limited data are available to assess its in vivo potential. Cytochalasin B was administered to Balb/c mice challenged i.d. with M109 murine lung carcinoma to determine whether the agent could affect an established i.d. tumor when the compound is administered s.c. in the region of the i.d. tumor, but not in direct contact with it. Cytochalasin B was also administered either i.p. or s.c. at a distant site or i.v. to determine whether it could affect the long-term development of an established i.d. tumor. Cytochalasin B was then liposome encapsulated to determine whether the maximum tolerated dose (MTD) of the compound could be increased, while reducing immunosuppression that we have previously characterized. Liposomal cytochalasin B was also administered to mice challenged i.d. with M109 lung carcinoma to assess its chemotherapeutic efficacy. The results can be summarized as follows: 1) cytochalasin B substantially delayed the growth of i.d. M109 tumor nodules, inhibited metastatic progression in surrounding tissues, and produced long-term cures in treated mice; 2) liposomal cytochalasin B increased the i.p. MTD by more than 3-fold, produced a different distribution in tissue concentrations, and displayed antitumor effects against M109 lung carcinoma similar to non-encapsulated cytochalasin B. These data show that cytochalasin B exploits unique chemotherapeutic mechanisms and is an effective antineoplastic agent in vivo in pre-clinical models, either in bolus form or after liposome encapsulation.

• Authors: Matthew Trendowski, Joan M Mitchell, Christine M Corsette, Christopher Acquafondata, Thomas P Fondy
• Journal: Investigational new drugs (Invest New Drugs) Vol. 33 Issue 2 Pg. 280-9 (Apr 2015) ISSN: 1573-0646 [Electronic] United States
• PMID: 25560541 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Liposomes
• Cytochalasin B

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology, therapeutic use)
• Cytochalasin B (administration & dosage, pharmacology, therapeutic use)
• Disease Progression
• Dose-Response Relationship, Drug
• Drug Administration Routes
• Liposomes (chemistry)
• Lung Neoplasms (drug therapy)
• Maximum Tolerated Dose
• Mice
• Mice, Inbred BALB C