Astragalin flavonoid inhibits proliferation in human lung carcinoma cells mediated via induction of caspase-dependent intrinsic pathway, ROS production, cell migration and invasion inhibition and targeting JAK/STAT signalling pathway

Abstract

The aim of the current study was to investigate the anti-lung cancer effects of astragalin. Studies were also undertaken to evaluate its effects on apoptosis induction, ROS production, cellular migration and invasion and JAK/STAT3 signalling pathway. MTT assay was used to evaluate cell viability in NSCLC A549 cells after exposure to astragalin molecule. Apoptosis was investigated using AO/EB staining, comet assay and western blotting assay. Fluorescence microscopy was implemented to estimate ROS production. Cell migration and invasion were measured using transwell chambers assay. Effects of astragalin on JAK/STAT pathway were investigated using western blotting assay. Results showed astragalin molecule induced inhibition of proliferation in A549 cells in a dose-dependent fashion. Further, the antiproliferative effects were found to mediate via apoptosis as suggested by AO/EB staining and western blotting assay. Astragalin modulated the expressions of caspase-3, caspase-9, Bax, Bak, Cyt-c Bcl-2, XIAP and Bcl-xL. Astragalin induced DNA damage in A549 cells which too indicated apoptotic cell death. Astragalin molecule enhanced the production of ROS by A549 cells. It inhibited both cell migration and invasion of A549 cells in a concentration-dependent manner. Finally, astragalin drug was observed with remarkable potential of targeting JAK/STAT pathway in A549 NSCLC cells. These results indicated that astragalin drug could prove helpful in lung cancer treatment and research provided more in-vivo studies are performed.

A hybrid nanopharmaceutical for specific-amplifying oxidative stress to initiate a cascade of catalytic therapy for pancreatic cancer

“…Together with apoptosis protease-activating factor 1 (Apaf-1) and autoactivated Caspase 9, cytochrome c can create an apoptosome that will activate Caspase 3 and carry out the apoptotic process [ 70 ]. More importantly, ROS is one of the causes of cell cycle arrest [ 71 ] and one of the multiple cytokines that the JAK/STAT signaling pathway [ 71 – 74 ] responds to (Fig. 3 A).…”

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran

“…Table 1 shows a comprehensive summary of these compounds and their distribution within the Morus alba L. tree. Against prostate [20] and ovarian cancer [21], as well as melanoma [21,22] Against colorectal [23], breast [24], gastric [25], and prostate cancer [26], as well as leukemia [27], and glioblastoma [ Against lung [28,29], gastric [30,31], colorectal [32], breast [33], kidney [34], ovarian [35], liver [36], and prostate cancer [37], as well as leukemia [38] and melanoma [39] Against cervical [42], breast [43][44][45], colorectal [46,47], gastric [48], prostate [49][50][51], lung [52][53][54], ovarian [55], liver [56,57], and pancreatic cancer [58], as well as melanoma [59] and renal cell carcinoma [60] Oxyresveratrol Against liver [64], lung [65,66], colorectal…”

Astragalin: a food-origin flavonoid with therapeutic effect for multiple diseases

“…Moreover, Xu et al reported that AG reduced the viability of human lung carcinoma cells and promoting apoptosis by inducing DNA damage, increasing the levels ofaspases-3, caspases-9, Bax, Bak, and Cyt-C, and decreasing Bcl-2, Bcl-xL, as well as XIAP. Besides, AG administration downregulated the expressions of p-JAK2, p-STAT1, and p-STAT3, diminished migration and invasion cell number, and upregulated the levels of ROS, which indicated that interfering with JAK/STAT signaling pathway might be a possible mechanism of AG to treat lung cancer ( Xu et al, 2021 ). In brief, these findings revealed that AG accelerated lung cancer cell death by inhibiting the growth and migration of cancer cell as well as inactivating the MAPK, NF-кB, and JAK/STAT signaling pathways.…”