Regulation of MAPKs Signaling Contributes to the Growth Inhibition of 1,7‐Dihydroxy‐3,4‐dimethoxyxanthone on Multidrug Resistance A549/Taxol Cells

Abstract

1,7-Dihydroxy-3,4-dimethoxyxanthone (XAN) is a bioactive compound isolated from Securidaca inappendiculata Hassk. and validated with antiproliferative activities on a panel of cancer cell lines. This study was designed to investigate its growth inhibitory effects on multidrug resistance (MDR) non-small cell lung carcinoma (NSCLC) cell line A549/Taxol and explore the possible linkage between modulation of MAPKs and the bioactivities. Its growth inhibitory potency on the cells was estimated by MTT assay, and flow cytometric analysis was employed to investigate its potential cell cycle arrest and proapoptosis effects. Expressions of hallmark proteins were assessed by Western-Blot method. The results showed A549/Taxol cells were sensitive to XAN. XAN inhibited the proliferation of A549/Taxol cells in the time and concentration dependent manners. It acted as a potent inducer of apoptosis and cell cycle arrest in the cells. Western-Blot investigation validated the proapoptosis and cell cycle arrest activities of XAN and the potential of MDR reversion. Upregulation of p38 by XAN, which accounted for the cell cycle arrest at G2 phase, and the downregulation of ERK associated with the proapoptosis activity were also revealed. Further analysis found p53 may be the central role mediated the bioactivities of MAPKs in A549/Taxol cells. Based on these evidences, a conclusion has been deduced that XAN could be a potential agent for MDR NSCLC therapy targeting specifically MAPKs.

Role of miR-584-5p in Lipopolysaccharide-Stimulated Human Bronchial Epithelial Cell Inflammation and Apoptosis

“…After transfection and LPS stimulation, the cells were digested with trypsin and centrifuged at 300 × g for 5 min. Before flow cytometric detection, the cells were washed carefully with phosphate-buffered saline (twice), fixed with 75% ethanol before storage at −20 °C overnight, and stained with propidium iodide solution (500 μ L) for 15 min at 30 °C for cell cycle analysis [ 17 ]. Apoptosis was determined by staining with Annexin V and PI (BD Biosciences, Franklin Lakes, NJ).…”

The use of African medicinal plants in cancer management

“…When administered at 10 mg/kg, the extracts augmented the lifespan of tumor-harboring mice by decreasing tumor cell viability ( Ngulde et al, 2019 ). Several active compounds have been identified in Securidaca longipendunculata including xanthones (muchimangins), methyl-salicylate, benzyl benzoates, bisdesmosidic saponins and triterpene saponins, of which xanthones have been implicated in antitumor and cytotoxic activities ( Mitaine-Offer et al, 2010 ; Dibwe et al, 2014 ; Zuo et al, 2016 ; Obasi et al, 2018 ; Klein-Júnior et al, 2020 ). Saponins in Securidaca longepedunculata induced apoptosis and inhibited the migration and invasion of cervical cancer cells ( Obasi et al, 2018 ).…”

“…Saponins in Securidaca longepedunculata induced apoptosis and inhibited the migration and invasion of cervical cancer cells ( Obasi et al, 2018 ). Xanthones of in S. longipedunculata impeded the proliferation of lung cancer cells and functioned as an elicitor of apoptosis ( Zuo et al, 2016 ).…”

Reversal effect of adenovirus-mediated human interleukin 24 transfection on the cisplatin resistance of A549/DDP lung cancer cells

“…P-gp overexpression can increase the rate at which drugs are pumped out of cells, which reduces the chemotherapeutic effects of the drugs, inducing drug resistance ( 12 , 13 ). Furthermore, tumor MDR mechanisms are associated with detoxification, repair and various signal transduction pathways ( 14 ). Generally, the drug resistance mechanisms in lung cancer are complex, involving many factors; therefore, it is considered highly important to identify efficient, low-toxicity methods of reversing lung cancer MDR.…”