Lactobacillus plantarum induces apoptosis in gastric cancer cells via modulation of signaling pathways in Helicobacter pylori

Abstract

Introduction: Gastric cancer is considered the second prevalent cause of death around the world. This type of cancer is generally induced by Helicobacter pylori which could colonize within the gastric mucosa of the infected cases. To date, triple antibiotic therapy has routinely been utilized for controlling the H. pylori-induced infection. However, this strategy has been unsuccessful, in large part because of issues such as occurring point mutations in the H. pylori genome that can induce resistance to the antibiotics administered. Recently, it has been shown that different probiotics may have strong anti-cancer effects, in which they are capable of inhibiting H. pylori by both immunological and non-immunological mechanisms. Here, we aimed at finding possible anticancer impacts of the probiotic bacterium Lactobacillus plantarum on gastric cancer, AGS cells. Methods: The anti-cancer effects of the conditioned media of the locally isolated L. plantarum on the AGS cells were evaluated by different analyses such as flow cytometry, DNA ladder assay, DAPI staining, and RT-PCR. Results: Our findings showed that the conditioned media of L. plantarum can inhibit both H. pylori and AGS cells through up-/down-regulation of PTEN, Bax, TLR4, and AKT genes. The exudates of the probiotic L. plantarum bacteria can increase the expression of PTEN, Bax, and TLR4, and also decrease the expression of AKT gene. Conclusion: In agreement with different reports, our results proved the anti-cancer effects of the locally isolated L. plantarum through some immunological cell signaling pathways. Accordingly, it seems the probiotics could be considered as at least a complementary treatment for different types of malignancies.

Overgrowth of Lactobacillus in gastric cancer

“…Lactobacillus shows anti-cancer activities. L. plantarum up-regulates the expression of PTEN , Bax , and TLR4 and down-regulates the AKT genes, and then promote the apoptosis of AGS cells[ 64 ]. In in vitro studies, L. gasseri causes a significant decrease in the expression of oncogenes including Bcl-2 , β-catenin, integrin α5, and integrin β1.…”

Probiotics mitigate Helicobacter pylori‐induced gastric inflammation and premalignant lesions in INS‐GAS mice with the modulation of gastrointestinal microbiota

“…Recently, several in vitro and in vivo studies showed the protective effect of Lactobacillus on colorectal cancer, due to its anti‐inflammatory and anti‐proliferative properties 7,8 . Researches in the stomach discovered that Lactobacillus could inhibit growth and induce apoptosis in gastric cancer cells 9 . The administration of Lactobacillus is indicated to compete with H. pylori and mitigate H. pylori ‐induced gastritis in mice 10 .…”

“…7,8 Researches in the stomach discovered that Lactobacillus could inhibit growth and induce apoptosis in gastric cancer cells. 9 The administration of Lactobacillus is indicated to compete with H. pylori and mitigate H. pylori-induced gastritis in mice. 10 However, the impact of Lactobacillus on H. pylori-induced carcinogenesis remains obscure.…”

Modulation of the PI3K/Akt/mTOR signaling pathway by probiotics as a fruitful target for orchestrating the immune response

“… 60 As shown in new report, Lactobacillus plantarum can inhibit both Helicobacter pylori colonization and a gastric cancer cell line (AGS) through the up-regulation of PTEN, BAX, TLR4, and the down-regulation of Akt genes. 30 Hence, blocking the hyperactivation of the PI3K/Akt/mTOR signaling pathway has emerged as a plausible therapeutic target for CRC and gastric cancers because of its involvement in cell growth and proliferation. However, the mechanisms of action involved in the beneficial effects of probiotics mediated through the PI3K/Akt/mTOR signaling pathway in GI disorders are not fully elucidated in relevant human models.…”