MTH1 Inhibitor TH287 Suppresses Gastric Cancer Development Through the Regulation of PI3K/AKT Signaling.

Background: Cancer cells evade oxidative stress through the MutT homologue-1 (MTH1), a member of the Nudix family. MTH1 maintains genome integrity and the viability of tumor cells. A new class of MTH1 inhibitors have attracted interest as anticancer agents, but their mechanisms of action remain poorly characterized. In this study, the authors evaluated the anticancer effects of the MTH1 inhibitor TH287 on gastric cancer (GCa) cells. Materials and Methods: BGC-823 and SGC-7901 cells were treated with TH287 and CCK-8, and colony-forming assays were performed. Cell migration was assessed through Transwell and scratch assays. Apoptotic status was measured via flow cytometry and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) staining. Cell cycle status was assessed by propidium iodide (PI) staining. The expression of PI3K/AKT signaling-related proteins was verified by western blotting. Results: TH287 inhibited cell viability, reduced cell proliferation, inhibited apoptosis, induced G2/M arrest, and suppressed cell migration. A loss of mitochondrial membrane potential and reduced Bcl-2/Bax expression were also observed in TH287-treated cells. These effects were mediated through the inhibition of pro-oncogenic PI3K/AKT signaling. Conclusions: These findings indicate that the MTH1 inhibitor TH287 mediates an array of anticancer effects in GCa cells through its effects on mitochondrial function and PI3K/AKT signaling. Collectively, these data highlight the promise of TH287 as a novel therapeutic option for GCa cells.

Hydrogen sulfide donor sodium hydrosulfide-improved heat tolerance in maize and involvement of proline.

Hydrogen sulfide (H2S) has long been considered as a phytotoxin, but nowadays as a cell signal molecule involved in growth, development, and the acquisition of stress tolerance in higher plants. In the present study, hydrogen sulfide donor, sodium hydrosulfide (NaHS), pretreatment markedly improved germination percentage of seeds and survival percentage of seedlings of maize under heat stress, and alleviated an increase in electrolyte leakage of roots, a decrease in tissue vitality and an accumulation of malondialdehyde (MDA) in coleoptiles of maize seedlings. In addition, pretreatment of NaHS could improve the activity of Δ(1)-pyrroline-5-carboxylate synthetase (P5CS) and lower proline dehydrogenase (ProDH) activity, which in turn induced accumulation of endogenous proline in maize seedlings. Also, application of proline could enhance endogenous proline content, followed by mitigated accumulation of MDA and increased survival percentage of maize seedlings under heat stress. These results suggest that sodium hydrosulfide pretreatment could improve heat tolerance of maize and the acquisition of this heat tolerance may be involved in proline.