Allicin inhibits the invasion of lung adenocarcinoma cells by altering tissue inhibitor of metalloproteinase/matrix metalloproteinase balance via reducing the activity of phosphoinositide 3-kinase/AKT signaling

Abstract

Abstract. Allicin, the main active principle associated with Allium sativum chemistry, has various antitumor activities. However, to the best of our knowledge, there is no available information to address the anti-invasive effect and associated mechanism in lung adenocarcinoma. In the present study, cell viability assay, cell adhesion assay, western blot analysis, Transwell migration and invasion assays and reverse transcription-quantitative polymerase chain reaction were performed. Allicin was identified to inhibit the adhesion, invasion and migration of lung adenocarcinoma cells in a dose-dependent manner, accompanied by decreasing mRNA and protein levels of matrix metalloproteinase (MMP)-2 and MMP-9. Conversely, the mRNA and protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were increased in a dose-dependent manner. Furthermore, it was revealed that allicin treatment significantly suppressed the phosphorylation of AKT (P<0.05), but not the total protein expression of AKT. Combined treatment with LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K)/AKT signaling, and allicin led to the synergistic reduction of MMP-2 and MMP-9 expression, followed by an increase in TIMP-1 and TIMP-2 expression. The invasive capabilities of lung adenocarcinoma cells were also suppressed. However, insulin-like growth factor-1 (an activator of PI3K/AKT signaling) reversed the effects of allicin on cell invasion and expression of MMP-2, MMP-9, TIMP-1 and TIMP-2. The present study concluded that allicin may inhibit invasion of lung adenocarcinoma cells by altering TIMP/MMP balance, via reducing the activity of the PI3K/AKT signaling pathway. This indicated that allicin may be recognized as an anti-invasive agent for lung adenocarcinoma treatment. IntroductionLung cancer is the predominant reason of cancer-associated mortality in developed and developing countries. Lung adenocarcinoma is the most common histological type of lung cancer, and accounts for ~50% of all lung cancers (1). Although the management and treatment of surgery, radiotherapy and chemotherapy have improved, the therapeutic efficacy is poor. One of the major reasons is the lack of adequate treatment against lung adenocarcinoma invasion (2,3). Therefore, the development of novel adjuvant therapeutic strategies specifically targeting the progression of invasion is of critical importance for improving the prognosis of patients with lung adenocarcinoma.Invasion occurs through a complex pathophysiological process involving multiple genetic alterations (4,5). Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in the invasion process of numerous malignant tumors by degrading the basement membrane and extracellular matrix (ECM) (6-8). Previous studies have suggested that MMP-2 and MMP-9 are associated with invasion in lung cancer (4,5). In addition, numerous studies have demonstrated that MMPs may be regulated by tissue inhibitor of metalloproteinase (TIMP) (6,9). Disturbing the balance of MMPs and TIMPs ma...

The Synergistic Antitumor Effect of 5-Fluorouracil Combined with Allicin against Lung and Colorectal Carcinoma Cells

“…In the present study, allicin inhibited migration and promoted cell death in the investigated lung and colorectal tumor cell lines [40,44]. The biological effects of allicin are attributed to the thiol groups.…”

“…Allicin 24h treatment was shown to be efficient in lung, breast, and colon cancer [42], and thyroid cancer [43]. Allicin can inhibit cell the migration and proliferation of lung adenocarcinoma after 24h treatment [40,44]. Furthermore, the 24h co-treatment of allicin combined with 5-FU showed that allicin sensitizes hepatocarcinoma cells to 5-FU, stimulating drug uptake [8].…”

Allicin Induces Electrogenic Secretion of Chloride and Bicarbonate Ions in Rat Colon via the TRPA1 Receptor

“…Allicin is produced from alliin (S-allylcysteine sulfoxide) by the enzyme, alliinase, upon tissue damage (1). Allicin has been shown to possess a variety of beneficial pharmacological and therapeutic effects, such as antimicrobial activity (2,3), anti-tumor effects (4), and the selective reduction of plasma lipid (triacylglycerol and LDL-cholesterol) concentrations (5).…”

Potential Therapeutic Value of Mangiferin for Lung Adenocarcinoma (Luad): A Comprehensive Study Based on in Vitro Experiments and Bioinformatics

“…For example, Zhang et al suggested 20(S)-protopanaxadiol (PPD) as a promising chemopreventive agent that downregulated the PI3K/Akt signaling pathway in A549 cells [68]. It was also indicated that allicin may inhibit invasion of LUAD by reducing the activity of the PI3K/AKT signaling pathway [69], and baicalein may increase cisplatin sensitivity of A549 cells via the PI3K/Akt/NF-κB pathway [70]. On the other hand, it was reported that mangiferin relieves lipopolysaccharide-induced injury by activating the PI3K/AKT pathway [71].…”