Modulation of cell-cell communication in the cause and chemoprevention/chemotherapy of cancer.
Chemopreventive or chemotherapeutic agents have been those that either kill cancer cells to a differential degree over the non-cancer cells or those chemicals that either block the induction of tumors in carcinogen-treated animals or retard transplanted tumors in animals. Carcinogenesis is a multi-stage, multi-mechanism process, involving the irreversible alteration of a stem cell ("initiation"), followed by the clonal proliferation of the initiated cell ("promotion"). To develop a strategy for intervention with chemoprevention/chemotherapeutic chemicals, the basic mechanism(s) of carcinogenesis must be understood. Gap junction intercellular communication (GJIC) regulates cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Normal cells have functional GJIC while cancer cells do not. Tumor promoters and oncogenes inhibit GJIC, while anti-tumor promoter and anti-oncogene drugs can reverse the down-regulation of GJIC. Transfection of gap junction genes (connexins) has been shown to reverse the tumorigenic phenotype. If prevention/treatment of cancer is to occur, prevention of the chronic down regulation of GJIC by tumor promoters in non-tumorigenic but initiated cells or the up-regulation of GJIC in stably down-regulated GJIC in tumor cells must occur to prevent or to treat cancers.
Trosko
J E
JE
National Food Safety and Toxicology Center, Department of Pediatrics and Human Development, Michigan State University, East Lansing 48824, USA. trosko@msu.edu
Chang
C C
CC
D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002273:Carcinogens / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects*; D018890:Chemoprevention; D017629:Gap Junctions / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*
D016588:Anticarcinogenic Agents; D002273:Carcinogens