Nádory plic - Nemalobuněčný karcinom - NSCLC

N-acetyl-glucosamine (GlcNAc)

A type of monosaccharide derived from chitosan,
Combined with TRAIL
Evaluated in vitro and in vivo
Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5.
Clinical samples expressed higher levels of DR5 than DR4,

GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis

By activating DR5 accumulation and clustering

In turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis

GlcNAc promoted DR5 clustering by improving its O-glycosylation.
GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis

Highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.

pubmed.ncbi.nlm.nih.gov/29533936/

Of the participants, 88,224 (19.4%) reported habitual glucosamine use at baseline. There were 9,366 cancer deaths during a median follow-up of 12.1 years, and we observed a significant association between the use of glucosamine and lower overall cancer mortality (HR = 0.95, 95% CI = 0.90–1.00, p < 0.05), kidney cancer (IRR = 0.68, 95% CI = 0.49–0.95, p < 0.05), lung cancer mortality (IRR = 0.84, 95% CI = 0.74–0.95, p < 0.05), and rectum cancer (IRR = 0.76, 95% CI = 0.59–0.98, p < 0.05). Subgroup analysis showed that habitual glucosamine supplementation was correlated with lower overall cancer mortality among participants who were aged ? 60 years, male, current smoker, without high cholesterol and not obese. Sensitivity analysis showed that the results were stable.

Conclusion: Habitual glucosamine use was significantly related to decreased overall cancer, kidney cancer, lung cancer, and rectum cancer mortality, based on data from the large-scale, nationwide, prospective UK Biobank cohort study.

Https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.947818/full

In DU145 cells glucosamine reduced the N-glycosylation of gp130, decreased IL-6 binding to cells and impaired the phosphorylation of JAK2, SHP2 and STAT3. Glucosamine acts in a very similar manner to tunicamycin, an inhibitor of protein N-glycosylation. Glucosamine-mediated inhibition of N-glycosylation was neither protein- nor cell-specific. Sensitivity of DU145, A2058 and PC-3 cells to glucosamine-induced inhibition of N-glycosylation were well correlated to glucosamine cytotoxicity in these cells.

ConclusionOur results suggested that the glucosamine-induced global inhibition of protein N-glycosylation might be the basic mechanism underlying its multiple biochemical and cellular effects.

Https://cancerci.biomedcentral.com/articles/10.1186/1475-2867-14-45

Paris Saponin I (PSI)

Steroidal saponin derivative extracted from a traditional Chinese herbal Paris polyphylla
Cytotoxic effects on several tumor cell lines.

Three non-small cell lung cancer (NSCLC) cells (H1299, H520, H460) and one small cell lung cancer (SCLC) cell (H446)

PSI significantly induced cell cycle arrest at the G2/M phase
mitochondrial-related apoptosis NSCLC cells but not SCLC cells
PSI reduced phosphorylation of AKT in NSCLC and ERK in SCLC in general.
Interestingly, we observed that PSI influenced different signaling pathways among the four kinds of lung cancer cells.
After PSI treatment, p38 MAPK and ERK activation were observed in H1299, while p38 MAPK increased and JNK decreased in H520.
JNK activation in H460 cells with PSI.
PSI upregulated the AKT activity and inhibited the JNK expression in H446 cells.
PSI exhibits the cytotoxicity in different pathways depending on the cancer types.
www.researchgate.net/publication/305482774_Paris_Saponin_I_inhibit_proliferation_and_promote_apoptosis_through_down-regulating_AKT_activity_in_human_non-small-cell_lung_cancer_cells_and_inhibiting_ERK_expression_in_human_small-cell_lung_cancer

Ubenimex Combined With Pembrolizumab, Nab-Paclitaxel, and Carboplatin

A Phase Study of Ubenimex Combined With Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non–Small-Cell Lung Cancer: TORG2241 (UBE-Q)