Oxymatrine induces A549 human non‑small lung cancer cell apoptosis via extrinsic and intrinsic pathways

Abstract

Oxymatrine is one of the primary natural compounds extracted from the Sophora flavescens, and has been reported to exhibit numerous pharmacological properties including cancer‑preventive and anti‑cancer effects, however the mechanisms as to how oxymatrine exhibits anti‑proliferative activity in non‑small cell lung carcinoma cells remains uncertain. The present study aimed to explore the mechanism of its anti‑cancer effect, and whether it is due to apoptosis induction and anti‑migration in the A549 lung cancer cell line. Detection of morphological alterations, MTT analysis, Hoechst/propidium iodide dual staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assays verified that oxymatrine induced A549 cell apoptosis. The caspase pan‑inhibitor z‑VAD‑FMK resulted in disappearance of oxymatrine‑elicited nuclei fragmentation via Hoechst 33342 staining. JC‑1 staining demonstrated a decrease in mitochondrial membrane potential which further verified the induction of apoptosis by oxymatrine. The caspase‑3, 8 and 9 activities of oxymatrine‑treated cells were activated, which suggested that extrinsic and intrinsic apoptotic pathways were involved in the anti‑proliferative effects of oxymatrine in A549 cells. Furthermore, the wound healing assay verified the anti‑migratory effects of oxymatrine in A549 cells.

Prodigiosin-Emerged PI3K/Beclin-1-Independent Pathway Elicits Autophagic Cell Death in Doxorubicin-Sensitive and -Resistant Lung Cancer

“…Another study showed crude extract of Neosartorya laciniosa KUFC 7896 and Neosartorya tsunodae KUFC 9213 potentiated doxorubicin tumoricidal activity by increasing Dox accumulation in lung cancer nuclei [ 37 ]. Of note, natural compounds such as curcumin and β-asarone from the Chinese herb Acorus tatarinowii [ 38 , 39 ] have showed their tumoricidal activity by reducing the Wnt/β-catenin signaling pathway, by enhancing current chemotherapeutic drugs, for example, curcumin and phloretin [ 40 , 41 ], and by inducing intrinsic or extrinsic apoptotic pathways, including waltonitone, matrine, oxymatrine, astragalin (kaempferol-3- O -β-d-glucoside), and 3- O -α-l-arabinosyl oleanolic acid from Schumacheria castaneifolia Vahl [ 42 , 43 , 44 , 45 , 46 ]. Some natural compounds’ inhibited growth factor have overcome drug resistance, for example, granulatimide, danorubicin, penicinoline, austocystin D, equol, kaempferol, resveratrol, ellagic acid, and butein [ 47 , 48 , 49 ].…”

Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model

“…Moreover, in combination with 5-fluorouracil, OMT can produce a synergistic anti-tumor effect both in vitro and in vivo [55]. Several recent studies have demonstrated the anticancer effects of OMT in diverse cancer cell lines such as prostate cancer [56], ovarian cancer [57], gastric cancer [58], colorectal cancer [59,60,61], breast cancer [62,63], bladder cancer [64], hepatocellular carcinoma [55], esophageal carcinoma [65], osteosarcoma [66,67], cervical cancer [68,69], gallbladder carcinoma [70], laryngeal carcinoma [71], hemangioma [72], lung cancer [73,74,75,76], synovial sarcoma [77], glioblastoma [78,79], and nasopharyngeal carcinoma [80]. The molecular mechanism(s) of action of OMT was found to be mediated by inducing cell cycle arrest and apoptosis and by causing an inhibition of angiogenesis and metastasis [57,64,81,82].…”

Purification, Preliminary Structure and Antitumor Activity of Exopolysaccharide Produced by Streptococcus thermophilus CH9

“…The fluorescent dye, Hoechst 33342, is widely used to stain DNA for evaluating apoptosis of viable cells. It is a blue fluorescent dye that can penetrate cell membranes and is less toxic to cells [ 28 , 29 ]. A small amount of Hoechst 33342 can enter normal cell membranes, so normal cells are light blue.…”