RESUMEN
OBJECTIVE: Melanoma, with its high degree of malignancy, stands as one of the most dangerous skin cancers and remains the primary cause of death from skin cancer. With studies demonstrating the potential of traditional Chinese medicine to intervene and treat melanoma, we turned our attention to celastrol. Celastrol is a triterpene compound extracted from the traditional Chinese medicine derived from Tripterygium wilfordii. Previous studies have shown that celastrol exerts inhibitory effects on various malignant tumors, including melanoma. Hence, our goal was to clarify the impact of celastrol on cell viability, apoptosis, and cell cycle progression by elucidating its effects on the PI3K/AKT/mTOR pathway. METHODS: CCK-8 and wound healing assays were used to determine the effect of celastrol on the viability and migration of B16-F10 cells. Changes in cell apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by flow cytometry. PI3K/AKT/mTOR pathway proteins and HIF-α mRNA expression in B16-F10 cells were detected by western blotting and qPCR. Moreover, the addition of a PI3K activator demonstrated that celastrol could inhibit the function of B16-F10 cells via the PI3K/AKT/mTOR pathway. RESULTS: Celastrol inhibited the viability and migration of B16-F10 cells. Through the inhibition of the PI3K/AKT/mTOR pathway down-regulates the expression of HIF-α mRNA, thereby causing an increase of ROS in cells and a decrease in the mitochondrial membrane potential to promote cell apoptosis and cell cycle arrest. The inhibitory effect of celastrol on B16-F10 cells was further demonstrated by co-culturing with a PI3K activator. CONCLUSION: Celastrol inhibits the function of B16-F10 cells by inhibiting the PI3K/AKT/mTOR cellular pathway and regulating the expression of downstream HIF-α mRNA.
RESUMEN
We sought to investigate the association between active cigarette smoking (ex- and current smokers) with or without exposure to biomass fuels and respiratory symptoms/lung function in middle-aged adults and the elderly. In the chronic obstructive pulmonary disease surveillance conducted in six cities of Guangdong province, China, we surveyed 1986 residents aged 40-93 years. We recorded respiratory symptoms, smoking status, use of biomass fuel, and other covariates by using a structured questionnaire. All models were adjusted for second-hand smoking. Active smoking with or without exposure to biomass fuels was significantly associated with wheezing, chronic cough, and phlegm (all P < .05). Active smoking alone with or without exposure to biomass fuels was associated with 2.5% and 0.6% reduction in the mean forced vital capacity predicted, 6.8% and 4.2% reduction in the mean forced expiratory volume in one second predicted, and 9.0% and 4.7% reduction in the mean maximal mid-expiratory flow predicted compared with the exposure to neither smoking nor biomass fuels, respectively. However, exposure to biomass fuel alone was associated with neither greater lung function impairment nor respiratory symptoms except for chronic cough. Efforts should be made to protect home owners and their family from adverse effects of indoor air pollution.
