Pyoluteorin Induces Apoptosis and Autophagy in NSCLC Cells

Abstract

Pyoluteorin is a natural occurring antibiotic and its anti-tumor activity has rarely been reported. This study aims to investigate the anti-tumor effects of pyoluteorin on human non-small cell lung cancer (NSCLC) cells. The cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was determined through caspase3 activity assay and immunoblotting. Autophagy was measured by transmission electron microscope (TEM) and immunostaining. The autophagy-related proteins were detected through immunoblotting. We found that pyoluteorin showed significant anti-tumor effects on human NSCLC cell lines H1299 (IC 50 1.57 µM) and H2030 (IC 50 1.94 µM). Moreover, pyoluteorin could induce apoptosis and autophagy as evidence by the upregulation of caspase3 activity, the accumulation of LC3 and expression of apoptosis or autophagy related proteins. In addition, pyoluteorin induced autophagy through c-Jun N-terminal kinase/B-cell lymphoma-2 (JNK/Bcl-2) signal pathway. Blocking JNK/Bcl-2 pathway significantly attenuated pyoluteorin-induced autophagy. Moreover, inhibition of autophagy by 3-methyladenine (3-MA) or Beclin1 knockout greatly promoted pyoluteorin-induced apoptosis and cell death. Our results showed that pyoluteorin could induce both apoptosis and autophagy in human NSCLC cells. Combination of pyoluteorin with autophagy inhibitior significantly promoted pyoluteorin-induced apoptosis and may be a potential anticancer strategy in the NSCLC therapy.

The Role of Pyoluteorin from Pseudomonas protegens Pf-5 in Suppressing the Growth and Pathogenicity of Pantoea ananatis on Maize

“…A similar study found that pyoluteorin inhibits Oomycetes, including Pythium ultimum , and contributes to the biocontrol of Pythium damping-off in cotton [ 26 ]. Pyoluteorin also has anti-tumor activity, which can induce cell cycle arrest and apoptosis in human triple-negative breast cancer cells [ 27 , 28 ]. Recently, pyoluteorin was reported to have activity against Chlamydomonas reinhardtii and Heterobasidion species [ 29 , 30 ].…”

Research Progress on the Anticancer Molecular Mechanism of Targets Regulating Cell Autophagy

“…When the JNK/Bcl-2 pathway is blocked, the pyoluteorin-induced autophagy is significantly reduced. The combination of pyoluteorin with the autophagy inhibitor 3-MA significantly promotes human non-small cell lung cancer cell death and therefore can be considered as a potential anticancer strategy in lung cancer therapy [128]. Betulin is a naturally occurring pentacyclic triterpene with several pharmacologic effects, such as anti-inflammatory, antiosteoclastogenic, antiamnesic, and anticancer properties.…”

Total Synthesis and Biological Investigation of Mindapyrroles A and B

“…[13] Pyoluteorin could induce apoptosis and autophagy in non-small cell lung cancer. [14] Although destruction of proton gradients is known for pyoluteorin, no work has been done on its ability to bind to and inhibit proteins. Protein binding of the structurally similar pyrrolomycins, marinopyrroles, and armeniaspirols has been investigated, and they have been shown to inhibit a variety of different macromolecules (Figure 1).…”

“…Additionally, pyoluteorin has been shown to have anti‐cancer effects via depolarization of mitochondrial membranes and accumulation of reactive oxygen species in triple negative breast cancer cells [13] . Pyoluteorin could induce apoptosis and autophagy in non‐small cell lung cancer [14] . Although destruction of proton gradients is known for pyoluteorin, no work has been done on its ability to bind to and inhibit proteins.…”