Biochemical modulation of tumor cell energy in vivo: II. A lower dose of adriamycin is required and a greater antitumor activity is induced when cellular energy is depressed Journal Article
| Authors: | Martin, D. S.; Stolfi, R. L.; Colofiore, J. R.; Dee Nord, L.; Sternberg, S. |
| Article Title: | Biochemical modulation of tumor cell energy in vivo: II. A lower dose of adriamycin is required and a greater antitumor activity is induced when cellular energy is depressed |
| Abstract: | A quadruple drug combination-consisting of a triple-drug combination of N-(phosphonacetyl)-L-aspartate (PALA) + 6-methylmercaptopurine riboside (MMPR) + 6-aminonicotanamide (6-AN), designed to primarily deplete cellular energy in tumor cells, + Adriamycin (Adria)-yielded significantly enhanced anticancer activity (i.e., tumor regressions) over that produced by either Adria alone at maximum tolerated dose (MTD) or by the triple-drug combination, against large, spontaneous, autochthonous murine breast tumors. The adenosine triphosphate (ATP)-depleting triple-drug combination administered prior to Adria resulted in a 100% tumor regression rate (12% complete regression; 88% partial regression) of spontaneous tumors. Histological examination of treated tumors demonstrated that the treatment-induced mechanism of cancer cell death was by apoptosis. The augmented therapeutic results (100% tumor regressions) were obtained with approximately one-half the MTD of Adria as a single agent and suggest the potential clinical benefit of longer, more effective, and safer treatment by low doses of Adria when combined with the triple-drug combination. Two likely mechanisms of action are discussed: (1) prevention of DNA repair; (2) complementary disruption of biochemical pathways by both the triple-drug combination and the biochemical cascade of apoptosis that is induced by a DNA-damaging anticancer agent such as Adria. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted. |
| Keywords: | controlled study; histopathology; doxorubicin; nonhuman; antineoplastic agent; mouse; animal; animal tissue; dna damage; apoptosis; animal experiment; animal model; tumor regression; dose-response relationship, drug; drug mechanism; drug therapy, combination; breast carcinoma; adenosine triphosphate; energy metabolism; aspartic acid; intravenous drug administration; mammary neoplasms, experimental; phosphonoacetic acid; intraperitoneal drug administration; cell energy; sparfosic acid; 6 aminonicotinamide; cancer; priority journal; article; methylthioinosine; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; 6 methylthioinosine; 6-aminonicotinamide; adenosine triphosphate depletion; cell strain cd8f1 |
| Journal Title: | Cancer Investigation |
| Volume: | 12 |
| Issue: | 3 |
| ISSN: | 0735-7907 |
| Publisher: | Informa Healthcare |
| Date Published: | 1994-01-01 |
| Start Page: | 296 |
| End Page: | 307 |
| Language: | English |
| DOI: | 10.3109/07357909409023028 |
| PROVIDER: | scopus |
| PUBMED: | 8187007 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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