Baicalin potentiates TRAIL-induced apoptosis through p38 MAPK activation and intracellular reactive oxygen species production

Abstract

The combination of tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) with other agents has been recognized as a promising strategy to overcome TRAIL resistance in cancer cells. Baicalin (5, 6‑dihydroxy‑7‑o‑glucuronide flavone) is a flavonoid from the root of the medicinal herb Scutellaria baicalensis Georgi, which has been reported to exert antioxidant, anti‑inflammatory, antiviral and anticancer activities in vitro. However, the effect of baicalin on TRAIL‑induced cytotoxicity has not been previously reported. In the present study, the effect of combining TRAIL and baicalin was investigated in non‑small cell lung cancer cell lines. The results revealed that baicalin was able to sensitize A549 and H2009 cells to TRAIL‑induced apoptosis. This was detected by the potentiation of poly‑adenosine‑5'‑diphosphate‑ribose polymerase cleavage and Annexin V‑fluorescein isothiocyanate staining of cells co‑treated with baicalin and TRAIL. In addition, p38 mitogen‑activated protein kinase was activated in baicalin and TRAIL co‑treated cancer cells, whereas the p38 inhibitor SB203580 effectively suppressed cell death within the co‑treated cells. Butylated hydroxyanisole and N‑acetyl‑cysteine, known reactive oxygen species (ROS) scavengers, significantly suppressed the potentiated cytotoxicity induced by baicalin and TRAIL co‑treatment. The present study is the first, to the best of our knowledge, to demonstrate that baicalin enhances the anticancer activity of TRAIL via p38 activation and ROS accumulation, and may be exploited for anticancer therapy.

Ferruginol induced apoptosis on SK-Mel-28 human malignant melanoma cells mediated through P-p38 and NF-κB

“…Phosphorylation of p38 is a signaling mechanism where most of the flavonoids exert their effect. 43,44 In the current study, we also found that FGL could induce phosphorylation of p38. RELA is a transcription factor.…”

Study of Baicalin toward COVID-19 Treatment: In silico Target Analysis and in vitro Inhibitory Effects on SARS-CoV-2 Proteases

“…9, 10) indicated involvements of MAPK, SYK, and PI3K as targets of baicalin. This result is in accordance with previously reported studies that baicalin inhibits p38 MAPK, and this mechanism may be responsible for its anti-inflammation effect [23,25,43,44]. MAPK is activated under the stress of cytokine; therefore, inhibiting MAPK is a promising approach for hyper-inflammatory disease, such as COVID-19 [45].…”

Antifungal Compounds againstCandidaInfections from Traditional Chinese Medicine

“…However, in mammalian cells (e.g., CHO cell), baicalin could reduce ROS production [ 69 ]. There are also reports showing that baicalin induces apoptosis in human non-small lung cancer cells and osteosarcoma cells through ROS production [ 70 , 71 ]. Baicalin could protect mitochondria from damage caused by streptozotocin and hepatic ischemia/reperfusion and increase the activity of citrate synthase in rats [ 72 , 73 ].…”