Lacticaseibacillus casei and Lacticaseibacillus rhamnosus cell-free supernatants induce apoptosis-related responses in PANC-1 human pancreatic cancer cells

Shadi  Moradi; Reza Moradi- Hajidavaloo; Fatemeh  Soleimanifar; Kiana  Shahzamani; Mehdi  Hajian; Hajar-Alsadat  Mansouri-Tehrani

doi:10.18502/ijm.v18i3.21651

Shadi Moradi Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
Reza Moradi- Hajidavaloo Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
Fatemeh Soleimanifar Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
Kiana Shahzamani Hepatitis Research Center, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
Mehdi Hajian Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
Hajar-Alsadat Mansouri-Tehrani Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

DOI: https://doi.org/10.18502/ijm.v18i3.21651

Keywords: Lacticaseibacillus casei; Lacticaseibacillus rhamnosus; Pancreatic cancer; BAX; BCL-XL

Abstract

Background and Objectives: This study aimed to evaluate the anticancer potential of Lacticaseibacillus casei and Lacti- caseibacillus rhamnosus cell-free supernatants (CFSs) against the PANC-1 human pancreatic cancer cell line, focusing on apoptosis, cell cycle modulation, and the expression of BAX and BCL-XL genes.

Materials and Methods: PANC-1 cancer cells and adult human dermal fibroblast (HDFa) cells were treated with various concentrations of individual or combined CFSs. Cell viability was assessed using the MTT assay. Apoptosis was evaluated through Hoechst/PI staining and flow cytometry, while cell cycle distribution was analyzed via flow cytometry. Gene expres- sion of BAX and BCL-XL was measured by quantitative real-time PCR.

Results: At 20% (v/v), all CFS treatments significantly reduced PANC-1 cell viability while showing minimal effects on HDFa cells. Flow cytometry confirmed apoptotic rates of 39.33%, 42%, and 40.33% for L. casei, L. rhamnosus, and their combination, respectively, alongside a notable increase in S-phase cell population. Gene expression analysis showed a pro-apoptotic shift, characterized by BAX upregulation and BCL-XL downregulation.

Conclusion: CFSs from L. casei and L. rhamnosus showed anticancer effects on PANC-1 cells, inducing apoptosis, S-phase arrest, and a favorable shift in apoptosis-related gene expression. These findings highlight their potential as promising adju- vant candidates for pancreatic cancer therapy.