Gypensapogenin I Suppresses Cell Proliferation in Triple-Negative Breast Cancer Via Triggering the Closure of AKT/GSK3β/β-Catenin and Notch-1 Signaling Pathways

Abstract

Jiaogulan (Gynostemma pentaphyllum) tea is a functional food that is commercially available worldwide. Gypensapogenin I (Gyp I), which is a natural damarane-type saponin, was obtained from the hydrolysates of total gypenosides. The present research was performed to investigate the potential antiproliferation effect of Gyp I in MDA-MB-231 cells and the underlying mechanisms. Here, we found that Gyp I attenuated survival, inhibited proliferation, and induced apoptosis in MDA-MB-231 cells. Target prediction by binding molecule docking and western blot assays confirmed the mechanism by which Gyp I inhibited the proliferation of breast cancer cells via the AKT/GSK3β/β-catenin signaling pathway. We also showed that Gyp I exhibited superior in vivo efficacy that was dose dependent. Tumor tissue transcriptome analysis indicated that Gyp I could decrease the expression levels of NOTCH1 and HES1, which was in contrast to the effect on MAML and NUMBL, indicating that our compound hindered the activation of the Notch-1 signaling pathway. In summary, we report for the first time that Gyp I shows excellent anti-breast cancer activity in vivo and in vitro and that its pathway of action is related to the AKT/GSK3β/β-catenin and Notch-1 signaling pathways. Therefore, Jiaogulan tea can not only be used as a health food but also possesses the possibility to treat triple-negative breast cancer (TNBC).

Eurochevalierines A–I, Sesquiterpene Alkaloid Hybrids with Anti-Triple Negative Breast Cancer Activity from Penicillium sp. HZ-5

“…Eurochevalierine D (4) was deduced to hold the molecular formula C 29 H 38 N 2 O 7 through its HRESIMS data analysis. The 1 H, 13 C, and DEPT NMR data demonstrated that compound 4 shared an analogous planar structure with 3. The delicate distinction between them were the absence of the hydroxyl at C-8a′ (δ C 43.9) in 4, and the configuration of Δ 5 ′ (13 ′ ) in 4 was E rather than Z in 3, which can be inferred by the HMBC correlations from H-4a′ to C-8a′, from H-1′ to C-8a′, and from H 3 -12′ to C-8a′, and the 1 H− 1 H COSY interactions of H-1′/H-8a′/H-4a′/H-8′, along with the NOESY correlations of H 2 -6′/ H 2 -14′ and H-4a′/H 3 -15′.…”

“…KBr) v max 3421, 2925, 1743, 1662, 1384, and 1233 cm −1 ; 1 H and13 C NMR data, see TableS3; HRESIMS m/z 533.2607 [M + Na] + (calcd. for C 29 H 38 N 2 O 6 Na, 533.2628).…”

Never in mitosis gene A-related kinase-8 promotes proliferation, migration, invasion, and stemness of breast cancer cells via β-catenin signalling activation

“…NEK8 knockdown also induced a decrease in the level of Akt phosphorylation at Ser473, which induced β-catenin phosphorylation at Ser552 47 , 55 (Fig. 6 M).…”

Gypenoside induces apoptosis by inhibiting the PI3K/AKT/mTOR pathway and enhances T-cell antitumor immunity by inhibiting PD-L1 in gastric cancer

“…A large number of studies have reported that gypenoside can induce morphological changes and apoptosis and inhibit the proliferation of various cancer cells, such as lung cancer ( Li et al, 2021 ; Qi et al, 2021 ), breast cancer ( Zu et al, 2021 ; Tan et al, 2022 ), and kidney cancer cells ( Liu et al, 2021 ). However, the effect of gypenoside on gastric cancer is unclear.…”