title: Overview how adenocarcinoma cancer cells avoid immune- and chemotherapy-induced apoptosis.
abstract: This review describes some aspects of uncontrolled tumor growth and development. In the past, it has been shown that colon adenocarcinomas use several tactics to avoid cell deletion and to maintain cell viability. In particular, colorectal cancer cells resist death ligands-induced apoptosis by expressing anti-apoptotic proteins. By direct interaction with FADD, the FLIP protein inhibits the signal transmission from death receptors to their cytoplasmic targets in COLO 205 cells. Colorectal cancer cells also stimulate own survival by inhibiting cytotoxic signals induced by interferons. Moreover, IFN-alpha increases immune-resistance of colon cancer cells by activation of NF-kappaB. Additionally, the cytoplasmic retention of proapoptotic protein clusterin also supports viability of cancer cells. Upon suitable stimulation normal cells are featured by clusterin translocation to the nucleus with concomitant cell death. We found that proapoptotic activity of clusterin is dependent on calcium ions, and depletion of intracellular calcium caused extensive death of COLO 205 cells. Other type of strategy to inhibit chemotherapy-dependent cell death is the activity of multidrug resistance proteins (MDR). These cell membrane efflux pumps actively expel the drugs from the cell interior to prevent their action on intracellular targets. The reversal of P-gp efflux pump in chemoresistant COLO 320 cell line was observed upon phenothiazine derivatives. The variety of antiapoptotic mechanisms in colorectal cancer cells makes anticancer therapy a great challenge but detailed knowledge of their complexicity gives promise to sensitize cancer cells to death stimuli.
authors.affiliation: Faculty of Veterinary Medicine, Warsaw Agricultural University, ul. Nowoursynowska 159, 02-776 Warsaw, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Pajak
authors.forename: A
authors.initials: A
authors.lastname: Orzechowski
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha