Iturin A‐like lipopeptides from Bacillus subtilis trigger apoptosis, paraptosis, and autophagy in Caco‐2 cells

Abstract

This study revealed that iturin A-like lipopeptides produced by Bacillus subtillis induced both paraptosis and apoptosis in heterogeneous human epithelial colorectal adenocarcinoma (Caco-2) cells. Autophagy was simultaneously induced in Caco-2 cells treated with iturin A-like lipopeptides at the early stage and inhibited at the later stage. A western blot analysis showed that the lipopeptides induced apoptosis in Caco-2 cells via a mitochondrial-dependent pathway, as indicated by upregulated expression of the apoptotic genes bax and bad and downregulated expression of the antiapoptotic gene bcl-2. The induction of paraptosis in Caco-2 cells was indicated by the occurrence of many cytoplasmic vacuoles accompanied by endoplasmic reticulum (ER) dilatation and mitochondrial swelling and dysfunction. ER stress also occurred with significant increases in reactive oxygen species and Ca 2+ levels in cells.Autophagy was detected by a transmission electron microscopy analysis and by upregulated expression of LC3-II and downregulated expression of LC3-I. The inhibition of autophagy at the later stage was shown by upregulated expression of p62. This study revealed the capability of iturin A-like B. subtilis lipopeptides to simultaneously execute antitumor potential via multiple pathways. K E Y W O R D Santicancer, apoptosis, autophagy, endoplasmic reticulum stress, iturin, lipopeptide, paraptosis

Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells

“…Paraptosis results in cytoplasmic vacuolation, and the number and size of vacuoles increase over time during paraptosis (21,26). In the irradiated KYSE-150 cells, the cytoplasmic vacuoles enlarged in size gradually, the nuclei were located peripherally, and subsequently, death-associated cellular detachment occurred (Fig.…”

“…Paraptosis differs from necrosis in that, paraptosis does not result in early plasma membrane rupture and the release of cellular contents (21,22). Recent studies have shown that paraptosis-associated cell death is an important anti-cancer mechanism of various natural products, and is a novel area of interest in cancer research (23)(24)(25)(26). It has been reported that photodynamic therapy may also induce paraptosis (27); however, aside from one report on colorectal cancer (16), radiation has not hitherto been associated with paraptosis.…”

Exopolysaccharides from probiotic bacteria and their health potential

“…The intrinsic pathway is indicated by the expression of caspase-3, caspase-9, BCl-2 and BAX, while, the extrinsic pathway is marked by the expression of caspase-8 and caspase-10. Among caspases, the caspase-8, caspase-9 and caspase-10 are initiators that are activated via binding to specific proteins; while caspase-3 is an effector caspase that is eventually activated by the active initiator caspases through photolytic cleavage [102,103]. Activation of Caspase-3 is often the indicator to confirm that the cancer cells have been subjected to cell shrinkage, nuclear fragmentation and chromatin condensation without affecting surrounding healthy tissues [104].…”

Immunomodulatory Role of Microbial Surfactants, with Special Emphasis on Fish

“…B. subtilis -derived iturin A induced both paraptosis and apoptosis in heterogeneous human epithelial colorectal adenocarcinoma (Caco-2) cells [ 68 ]. Iturin concurrently induced autophagy in Caco-2 cells treated at an early stage but inhibited autophagy at the later stages.…”

“…Iturin concurrently induced autophagy in Caco-2 cells treated at an early stage but inhibited autophagy at the later stages. They showed that upregulated expression of p62 was linked to the inhibition of autophagy at the later stages, and iturin-driven anti-tumor activity was executed via multiple pathways [ 68 ]. Lipopeptides kill cancer cells via various mechanisms.…”