Nucleoside diphosphate Kinase-Dependent Suppression of Apoptosis in Esophageal Cancer Cells by the Oral Pathogen Porphyromonas Gingivalis

Esophageal cancer is the eighth most frequent tumor and sixth leading cause of cancer death globally. Recent evidence suggests that a Gram negative, anaerobic bacterium that is a causative agent of periodontitis, Porphyromonas gingivalis, is strongly associated with esophageal cancer. Indeed, P. gingivalis infection strongly correlates with disease stage and survival time. However, the potential mechanisms by which this important oral pathogen may predispose to the development of esophageal cancer are entirely unknown. It has previously been established that P. gingivalis produces a nucleoside diphosphate kinase (NDK) that can promote epithelial cell survival by hydrolyzing extracellular ATP and preventing apoptosis initiated by the purinergenic receptor, P2X7. Therefore, we set out to determine if P. gingivalis was able to inhibit druginduced apoptosis in esophageal cancer (KYSE-30) cells, hypothesizing that this phenomenon may be dependent upon a functional ndk gene. Campothecin, derivatives of which are being tested for treatment of esophageal cancer, induced apoptosis in KYSE-30 cells. Infection with wild type P. gingivalis inhibited CAMP-induced esophageal cancer cell death, whereas ndkdeficient P. gingivalis mutants were less efficient in blocking apoptosis. Therefore, the epidemiological association noted between P. gingivalis and esophageal cancer may be partly explained by NDK-dependent inhibition of apoptosis