Autophagy as well as apoptosis is an emerging target for cancer therapy. Wogonin, a flavonoid compound derived from the traditional Chinese medicine of Huang-Qin, has anticancer activity in many cancer cells including human nasopharyngeal carcinoma (NPC). However, the involvement of autophagy in the wogonin-induced apoptosis of NPC cells was still uninvestigated. In this study, we found wogonin-induced autophagy had interference on the process of apoptosis. Wogonin-induced autophagy formation evidenced by LC3 I/II cleavage, acridine orange (AO)-stained vacuoles and the autophagosome/autolysosome images of TEM analysis. Activation of autophagy with rapamycin resulted in increased wogonin-mediated autophagy via inhibition of mTOR/P70S6K pathway. The functional relevance of autophagy in the antitumor activity was investigated by annexin V-positive stained cells and PARP cleavage. Induction of autophagy by rapamycin ameliorated the wogonin-mediated apoptosis, whereas inhibition of autophagy by 3-methyladenine (3-MA) or bafilomycin A1 increased the apoptotic effect. Interestingly, this study also found, in addition the mTOR/P70S6K pathway, wogonin also inhibited Raf/ERK pathway, a variety of Akt pathways. Inactivation of PI(3) K/Akt by their inhibitors significantly induced apoptosis and markedly sensitized the NPC cells to wogonin-induced apoptosis. This anticancer effect of Akt was further confirmed by SH6, a specific inhibitor of Akt. Importantly, inactivation of its downstream molecule ERK by PD98059, a MEK inhibitor, also induced apoptosis. This study indicated wogonin-induced both autophagy and apoptosis through a variety of Akt pathways and suggested modulation of autophagy might provide profoundly the potential therapeutic effect.

There is limited literature analyzing the outcome of human poisoning with methomyl and cypermethrin pesticide mixture. Between 2002 and 2018, a total of 63 patients intoxicated with methomyl, cypermethrin, or their pesticide mixture were treated at Chang Gung Memorial Hospital. The patients were categorized into three groups based on the type of pesticide, as methomyl (n = 10), cypermethrin (n = 31), or methomyl and cypermethrin (n = 22). Demographic, clinical, laboratory, and mortality data were obtained for analysis. The patients were aged 54.9 ± 18.9 years. Following ingestion, the patients experienced a wide range of clinical symptoms, including aspiration pneumonia (50.8%), acute respiratory failure (41.3%), acute kidney injury (33.3%), multiple organ failure (19.0%), emesis (19.0%), acute hepatitis (12.7%), diarrhea (7.9%), seizures (4.8%), lacrimation (4.8%), etc. After analysis, it was found that patients with methomyl and cypermethrin poisoning suffered higher incidences of acute respiratory failure (p < 0.001), aspiration pneumonia (p = 0.004), acute kidney injury (p = 0.011), and multiple organ failure (p < 0.001) than the other groups. Laboratory analyses revealed that patients with methomyl and cypermethrin poisoning had a higher creatinine level (p = 0.011), white blood cell count (p < 0.001), and neutrophil count (p = 0.019) than the other groups. A total of seven (11.1%) patients died. The average duration of hospitalization was 9.8 ± 10.0 days. In a multivariate logistic regression model, it was revealed that methomyl pesticide (p = 0.045) or methomyl and cypermethrin pesticide mixture (p = 0.013) were significant risk factors for acute respiratory failure. Nevertheless, no mortality risk factor could be identified. Therefore, the analytical results suggest that methomyl pesticide is the major contributor to the toxicity of methomyl and cypermethrin pesticide mixture poisoning. More research is needed.