A novel anticancer agent SNG1153 inhibits growth of lung cancer stem/progenitor cells

Abstract

Lung cancer is the leading cause of cancer-related death in both men and women. Lung cancer contains a small population of cancer cells with stem-like features known as cancer stem cells (CSCs). CSCs are often more resistant to current therapeutic treatments. Thus, it is urgent to develop a novel agent that is able to inhibit CSCs growth. In this study, we examined the ability of SNG1153, a novel chemical agent to inhibit the growth of lung CSCs. We found that SNG1153 inhibited growth and induced apoptosis in established lung cancer cells. We also found that SNG1153 inhibited the tumorsphere formation and decreased CD133-positive (lung CSC marker) cancer cells. SNG1153 was able to attenuate tumor formation in NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice injected with lung tumorsphere cells. We further demonstrated that SNG1153 induced β-catenin phosphorylation and down-regulated β-catenin. Our results thus demonstrate that SNG1153 effectively inhibits the growth of lung CSCs and suggest that SNG1153 may be a novel therapeutic agent to treat human lung cancer.

Natural Products Targeting Cancer Stem Cells for Augmenting Cancer Therapeutics

“…It also inhibited the growth of lung CSCs, which may be a novel therapeutic agent to treat human lung cancer. SNG1153 induced β-catenin phosphorylation and downregulated β-catenin [ 101 ].…”

N-Ethyl-N-Nitrosourea Induced Leukaemia in a Mouse Model: Protective Effect of Icaritin via Inhibition of IL-6/JAK2/STAT3 Pathway Causes Apoptosis

“… 22 Moreover, ICT has been shown to induce apoptosis in human endometrial cancer cells by modulating apoptotic proteins and inhibiting specific signaling pathways, such as the PI3K/Akt and MAPK pathways. 23 Additionally, in vitro and in vivo studies have demonstrated that ICT can suppress leukemia’s MAPK, AKT, and JAK2/STAT3 signaling pathways. 24 Although previous studies have explored the effects of ICT in various biological systems and its potential as a therapeutic agent for leukemia, there is a lack of research specifically focusing on the efficacy of ICT in ENU-induced leukemia and its relationship with the IL-6/JAK2/STAT3 signaling pathway.…”

Synergistic SNGI-TKI combination against LSCs

“…Mechanistically, Icaritin (SNG162) and a newly developed analog of Icaritin (SNG1153), with enhanced potency and specificity, have been demonstrated to target key signaling proteins and regulate multiple cell signaling and survival pathways in different types of cancer cells. For example, it has been reported that SNG1153 inhibits growth and induces apoptosis in lung cancer cells, including CSCs, by disrupting WNT/β-catenin signaling through induction of β-catenin phosphorylation and protein degradation in these cells [ 6 ]. SNG inhibitors (SNGI) also inhibit multiple myeloma and hepatocellular carcinoma initiation by inactivating the IL-6/JAK2/STAT3 pathway [ 7 ].…”