Effect of the drug Lonidamine on Chinese hamster ovary cells in vitro and on experimental tumors
Hypoxic cells in solid tumors are known to be resistant to radiation, and may also be resistant to some anti-cancer drugs. Biochemical properties of hypoxic cells, such as their dependence on anaerobic glycolysis leading to production of lactate and low pH might have potential for inhibition by drugs with selective activity against hypoxic cells. Such drugs might improve the Therapeutic Index when used with radiation or some conventional anti-cancer drugs. Lonidamine, an inhibitor of mitochondrially-bound hexokinase and lactate transport, was cytotoxic to CHO cells at low pH, but had no effect at physiological pH under aerobic or hypoxic conditions. Lonidamine has also been tested for in vivo effects against three murine tumors: the KHT fibrosarcoma, 16/C mammary carcinoma and the Lewis Lung Tumor. The drug was tested either alone, or with radiation or Adriamycin to kill aerobic cells, and/or with glucose and insulin to lower intra-tumor pH. No major therapeutic effects have been demonstrated.
- Research Organization:
- Univ. of Toronto, Ontario
- OSTI ID:
- 6004773
- Report Number(s):
- CONF-8311204-
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 10:9; Conference: Conference on chemical modifiers of cancer treatment, Banff, Alberta, Canada, 27 Nov 1983
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
AMINES
RADIOSENSITIVITY EFFECTS
CELL KILLING
RADIOINDUCTION
CHO CELLS
BIOLOGICAL RADIATION EFFECTS
EXPERIMENTAL NEOPLASMS
ANOXIA
CARBOXYLIC ACIDS
CARCINOMAS
DOXORUBICIN
FIBROSARCOMAS
GLYCOLYSIS
IN VITRO
X RADIATION
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
CHEMICAL REACTIONS
DECOMPOSITION
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
IONIZING RADIATIONS
NEOPLASMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
RADIATION EFFECTS
RADIATIONS
SARCOMAS
560121* - Radiation Effects on Cells- External Source- (-1987)
560152 - Radiation Effects on Animals- Animals