TR35 Exerts Anti-tumor Effects by Modulating Mitogen-Activated Protein Kinase and STAT3 Signaling in Lung Cancer Cells

Abstract

Cancer is a complex disease extremely dependent on its microenvironment and is highly regulated by a variety of stimuli inside and outside the cell. Evidence suggests that active camel whey fraction (TR35) confer anti-tumor effects in non-small cell lung cancer (NSCLC). However, its exact mechanisms remain elusive. Here, we investigated the mechanisms underlying suppression of NSCLC cell growth and proliferation by TR35. Treatment of A549 and H1299 cells with TR35 suppressed their growth and enhanced apoptosis, as revealed by CCK-8, colony formation and flow cytometric analyses. We find that TR35 suppresses tumor growth in a xenograft nude mouse model without losses in body weight. RNA-seq and KEGG pathway analyses showed that the DEGs were enriched in mitogen-activated protein kinase (MAPK) and Jak-STAT signaling pathways. After test the key factors’ activity associated with these pathways by Immunohistochemical (IHC) staining and western blotting, the activation of JNK phosphorylation and inhibition of p38 and STAT3 phosphorylation was observed both in TR35 treated lung cancer cell and tumor tissue. Taken together, these results showed that TR35 play a significant role in the NSCLC progression in the tumor microenvironment via MAPK and Jak-STAT signaling, highlighting TR35 as a potential therapeutic agent against lung cancer.

Camels’ biological fluids contained nanobodies: promising avenue in cancer therapy

“…Nanobodies were reported in camels in the early 1980s, the presence of which makes camels unique. Importantly, camel milk contains nanobodies that potentially can be used as a promising tool for diagnosing and targeting metastatic cancers [36][37][38][39].…”

“…Furthermore, the active camel whey fraction (TR35) was found to display anti-tumorigenic effects in non-small lung cancer. This was accomplished through promoting in vitro cancer cells apoptosis and inhibiting tumour growth in vivo model via activation of JNK phosphorylation and suppression of P38 and STAT3 phosphorylation [39]. The tumours battling power provided by the camel milk were validated by numerous in vitro and in vivo investigations [59][60][61][62][63].…”

Quality characteristics and nutrient contents of Bactrian camel milk as determined by mid‐infrared spectroscopy

“…Accordingly, camel milk has high application value, especially as a substitute for hypoallergenic infant formula (Maryniak et al 2018). Furthermore, it exhibits anti-inflammation (Al-Omari et al 2019;Patel et al 2021), anti-hypertension, antidiabetes (Mudgil et al 2018) and anti-cancer activities (El-Kattawy et al 2021;Shi et al 2021) as well as having important medical value in the treatment of liver and kidney injury (Usman et al 2020;Dou et al 2022). Milk composition is an important indicator reflecting the quality of dairy products and the health status of dairy animals.…”

Lack of SIRP‐alpha reduces lung cancer growth in mice by promoting anti‐tumour ability of macrophages and neutrophils

“…p38 MAPK and STAT3 signalling are activated in most of cancer cells and participate in cancer cell proliferation and metastases 21,22 . Suppression of p38 MAPK and STAT3 activation was associated with reduced lung cancer growth in vitro and in animal models 23,24 . However, the role and downstream signalling pathways of SIRPα in the progression of lung cancer are not well studied so far.…”

“… 21 , 22 Suppression of p38 MAPK and STAT3 activation was associated with reduced lung cancer growth in vitro and in animal models. 23 , 24 However, the role and downstream signalling pathways of SIRPα in the progression of lung cancer are not well studied so far. We in this study, for the first time, investigated the role of SIRPα in SIRPα knock‐out (KO) mice and found that lack of SIRPα significantly reduced lung cancer cell growth in mice, in association with improved MPs and neutrophils (NPs) phagocytosis and reduced IL‐6 expression in tumour tissues.…”