Introduction
Signal transducers and activators of transcription (STAT) family consists of seven diverse members, named STAT1 to STAT6, STAT5a, and STAT5b [
1,
2]. Accumulated evidences have indicated that STAT members can exhibit diverse actions under both physiological and pathological conditions [
3,
4,
5,
6,
7]. Of the STAT family members, STAT3 and STAT5 can regulate various hallmarks that are closely associated with tumorigenesis [
8,
9,
10,
11,
12,
13].
Phosphorylation of STATs can be driven via the stimulation of Janus-activated kinases (JAK) and Src families of proteins [14,15,16]. The activation can promote their homodimerization, movement into the nucleus, DNA binding, thus leading to transcription of oncogenic genes [
4,
17,
18]. Interestingly, protein tyrosine phosphatases (PTPs) such as SHP-1, SHP-2, PTPε, and PTEN can negatively regulate the STAT signaling pathway [
19,
20,
21]. In addition, various previous reports have indicated that a number of naturally derived pharmacological agents can attenuate STAT activation, which may have a great potential in the prevention and therapy of cancer [
13,
22,
23,
24,
25,
26].
Gastric cancer remains a lethal disease [
25,
27,
28,
29]. It has emerged as a significant health problem characterized by poor prognosis and disease relapse [
30,
31,
32].
Gastric cancer has been treated using different strategies such as surgery, chemotherapy, and radiation therapy, but the
clinical outcome has been not quite effective with development chemoresistance being a major obstacle [
31,
33,
34,
35,
36,
37].
Hence, elucidation of the biological characteristics and molecular mechanisms of novel agents may be beneficial for the gastric cancer treatment. As the abnormal expression and dysregulation of STAT3/5 have been reported in various malignancies including gastric cancer [
38],
targeting of STAT3/5 phosphorylation may be beneficial for gastric cancer treatment.
A number of agents isolated from medicinal plants have been used for treatment against diverse malignancies [
39,
40,
41,
42]. Albendazole (Methyl 5-(propylthio)-2-benzimidazolecarbonate)) carbamate, ABZ), a well-known benzimidazole derivative carbamate anthelminthic [
43], can target helminth cell proliferation through disputing microtubule assembly and affecting glucose uptake [
44,
45].
ABZ has been reported to exhibit diverse anticancer actions against several tumor cell lines such as hepatocellular carcinoma, colorectal cancer, non-small cell lung cancer, as well as cutaneous squamous cell carcinoma [46,47,48,49]. For instance, ABZ was reported to be effective against non-small cell lung cancer cells by reducing both vascular endothelial growth factor (VEGF and hypoxia-inducible factor-1-α (HIF-1-α) activities [48]. It was also found to promote apoptosis in human leukemia cells by causing TNF-α upregulation [50]. However, the influence of ABZ on gastric cancer cells and the underlying mechanisms have not been evaluated previously. In this study, it was investigated whether ABZ can impact the activation of STAT3 and STAT5 pathway in gastric cancer cells and thereby exhibit pleiotropic actions on tumor progression as well as survival.