Salmonella induce autophagy in melanoma by the downregulation of AKT/mTOR pathway

Abstract

Salmonella have been demonstrated to inhibit tumor growth. However, the mechanism of Salmonella-induced tumor cell death is less defined. Autophagy is a cellular process that mediates the degradation of long-lived proteins and unwanted organelles in the cytosol. Tumor cells frequently display lower levels of basal autophagic activity than their normal counterparts and fail to increase autophagic activity in response to stresses. Autophagy is involved in the cell defense elimination of bacteria. The signaling pathways leading to activation of Salmonella-induced autophagy in tumor cells remain to be elucidated. We used autophagy inhibitor (3-Methyladenine) and apoptosis inhibitor (Z-VAD-FMK) to demonstrate that Salmonella may induce cell death via apoptosis and autophagic pathway. Meanwhile, we suggested that Salmonella induce autophagy in a dose- and time-dependent manner. The autophagic markers were increased after tumor cell infected with Salmonella. In addition, the protein express levels of phosph-protein kinase B (P-AKT), phosph-mammalian targets of rapamycin (P-mTOR), phosph-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells were decreased by western analysis after Salmonella infection. In conclusion, our results point out that Salmonella induce the autophagic signaling pathway via downregulation of AKT/mTOR pathway. Herein, our findings that Salmonella in controlling tumor growth may induce autophagic signal pathway.

Salmonella as an Innovative Therapeutic Antitumor Agent

“…The AKT/mTOR/p70S6K signaling pathway negatively regulates autophagy. We determined that the levels of phosphorylated AKT, mTOR, and p70S6K were significantly decreased in Salmonella -treated tumor cells [30]. These results showed that Salmonella can induce autophagic activities in addition to caspase-dependent cell death in tumor cells (Figure 2).…”

Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes

“…Autophagic flux is a method that is used to measure autophagy, which is always assessed using MAP1LC3B/LC3 and SQSTM1/p62 western blotting [10]. PI3K/AKT/mTOR is the most important intracellular signal pathway to negatively regulate autophagy [11][12][13]. In addition, MAPKs, a family of serine/threonine protein kinases, are also involved in the process of autophagy [14,15].…”

Bacterial xenophagy and its possible role in cancer: A potential antimicrobial strategy for cancer prevention and treatment

“…typhimurium induces xenophagic activation in melanoma cells via downregulation of the AKT-MTOR-RPS6KB/p70S6K pathway. 76 When Salmonella accumulates in tumor sites, cancer cells try to induce a strong xenophagic response to eliminate the bacteria, resulting in the inhibition of tumor growth, which is associated with the induction and processing of the autophagy marker LC3. 76 Another study from Liu, et al showed that tumor-targeting Salmonella A1-R or Salmonella strain VNP20009 induce xenophagy in human liver cancer cells, which serves a protective role for infected cancer cells.…”

“…76 When Salmonella accumulates in tumor sites, cancer cells try to induce a strong xenophagic response to eliminate the bacteria, resulting in the inhibition of tumor growth, which is associated with the induction and processing of the autophagy marker LC3. 76 Another study from Liu, et al showed that tumor-targeting Salmonella A1-R or Salmonella strain VNP20009 induce xenophagy in human liver cancer cells, which serves a protective role for infected cancer cells. Knockdown of essential autophagy genes ATG5 or BECN1 in bacteria-infected cancer cells leads to a significant increase of intracellular bacteria multiplication in cancer cells and further retards cancer cell growth.…”