L-securinine inhibits the proliferation of A549 lung cancer cells and promotes DKK1 promoter methylation

Abstract

Abstract. L-securinine is a natural product extracted and isolated from the leaf of dried Securinega suffruticosa. The aim of the present study was to explore the effects of L-securinine on proliferation, and the methylation profile of the dickkopf-related protein 1 (DKK1) gene in human lung cancer cells and fibroblasts. L-securinine was extracted, isolated and the structure was identified. The cytotoxicity of L-securinine in A549 cells was evaluated by Cell Counting Kit-8 assays. The expression and DNA methylation profile of DKK genes was analyzed by reverse transcription-quantitative polymerase chain reaction and bisulfite sequencing polymerase chain reaction, respectively. L-securinine inhibited the proliferation of lung cancer cells; the half-maximal inhibitory concentration values were 8.92, 4.73 and 3.81 µg/ml, at 24, 36 and 48 h post-treatment, respectively. DKK1, 2 and 3 expression was significantly increased in A549 cells compared with HLF-a cells. L-securinine induced the downregulation of DKK1 in A549 cells in a dose-dependent manner and induced methylation changes at CpG sites in the DKK1 promoter region. L-securinine may be a potential anticancer drug that mediates its effects by altering DKK1 gene methylation.

Diversity and antimicrobial activity of endophytic fungi isolated from Securinega suffruticosa in the Yellow River Delta

“…Pharmacological studies have shown that S. suffruticosa can promote blood circulation, relax the muscles and tendons, invigorate the spleen and kidney, and relieve rheumatic pains. Moreover, this shrub is effective for the treatment of neurasthenia, facial nerve paralysis, post-polio syndrome, dizziness, deafness, narcolepsy, impotence, and acute liver injury, and other diseases [7][8][9][10]. It possesses an extremely high application value [4].…”

Securinine suppresses osteoclastogenesis and ameliorates inflammatory bone loss

“…Sec has been developed as a drug to treat neurological conditions such as ALS, polio, and multiple sclerosis (Buravtseva, 1958). Moreover, recent studies have shown that Sec has inhibitory effects on human lung cancer through cytotoxicity in A549 cells (Han et al, 2017). However, the effect of Sec on bone-resorbing osteoclasts in bone metabolism remains unknown.…”

Biologically active indolizidine alkaloids

“…In addition, the compound induced dose‐dependent downregulation of Dickkopf‐related protein 1 (DKK1) in A549 cells as well as altered methylation of CpG sites in the DKK1 promoter region. Thus, this alkaloid may be a potential antitumor agent that acts by altering the methylation of the DKK1 gene 151 . Furthermore, securinine inhibited both purified thioredoxin and thioredoxin reductase in intact cells 49 .…”

“…Securinine ( 13 , Figure 4C), a major tetracyclic indolizidine alkaloid isolated from the plant Securinega suffruticosa , has shown anticancer activity in many studies 48,150 . Against A549 lung cancer cells treated for 24, 36, and 48 h, the half‐maximal antiproliferative concentration values of securinine were 8.92, 4.73, and 3.81 μg/ml, respectively 151 . In addition, the compound induced dose‐dependent downregulation of Dickkopf‐related protein 1 (DKK1) in A549 cells as well as altered methylation of CpG sites in the DKK1 promoter region.…”