Pseudomonas aeruginosa-Mannose Sensitive Hemagglutinin-based Treatment Strategy for Liver Cancer

Abstract

Background: Although it does not represent a threat to healthy humans, Pseudomonas aeruginosa is a type of aerobic, gramnegative bacteria that can cause catastrophic infections in patients with immune system abnormalities and cystic fibrosis.Objectives: The current study investigated the effect of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) on liver cancer cell viability, colony formation, and invasion potential, and explored the underlying mechanism.Materials and Methods: Proliferation potential and clonogenic survival of the cells were studied using MTT and colony formation assays, respectively. Transwell and Western blotting assays were used for the assessment of invasive potential and protein expression, respectively.Results: The results revealed that exposure to PA-MSHA led to a time-dependent suppression in HepG2 and HEP3B cell proliferation. Incubation with PA-MSHA decreased HepG2 cell proliferation to 92%, 75%, 50%, 35%, and 20%, respectively, after 12, 24, 36, 48, and 72 hours. Similarly, incubation for 12, 24, 36, 48, and 72 hours reduced the proliferation of HEP3B cells to 94%, 79%, 55%, 41%, and 26%, respectively. The rate of clonogenic survival was significantly lower in HepG2 and HEP3B cells on incubation with PA-MSHA. The cell invasion potential was also significantly reduced on incubation with PA-MSHA. In HepG2 cells, incubation with PA-MSHA significantly reduced the expression of Bcl-2 (26 kDa) protein and promoted Bax (21 kDa) level. Following incubation with PA-MSHA, HepG2 cells showed higher cleaved caspase-3 level compared to the control cells. Compared to control cells, the PA-MSHA incubation of HepG2 cells resulted in a prominent reduction in Notch3 protein expression.Conclusion: In summary, PA-MSHA treatment prevents liver cancer cell proliferation and targets the survival of clonogenic cells. It reduces invasiveness, targets Notch3 protein expression in liver cancer cells, and increases the level of proapoptotic and suppresses antiapoptotic protein expression. Therefore, PA-MSHA shows encouraging anticancer effects on HepG2 and HEP3B cancer cells, suggesting that it could be developed as a viable treatment option for liver cancer.

Keywords: Pseudomonas aeruginosa-mannose sensitive hemagglutinin; viability; apoptosis; liver cancer; anticancer