DG-8d, a novel diosgenin derivative, decreases the proliferation and induces the apoptosis of A549 cells by inhibiting the PI3k/Akt signaling pathway

Wang, Wenbao; Chen, Zhe; Rothenberg, Marc E.; Ni, Shiyu; Jia, Yongming; Fan, Li; Ma, Liwei

doi:10.1016/j.steroids.2021.108898

Cited by 7 publications

(3 citation statements)

References 36 publications

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“…(Jag et al2009). As a well-characterized transcription factor, the target genes of FoxO family are involved in various physiological processes such as cell cycle, apoptosis and metabolism (Lee et al 2017;Wang et al 2021). Therefore, the abnormal insulin signal in the ovary may be associated with a variety of biological effects.…”

Section: Discussionmentioning

confidence: 99%

Network Analysis Suggests Ovarian Insulin Hypersensitivity Contributes to Depressed Viability of Ovarian Cells in PCOS Women

Wang,

Yang

et al. 2024

Preprint

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Purpose Polycystic ovarian syndrome (PCOS) is a global health-threatening endocrinopathy that causes infertility in women. Although peripheral insulin resistance has been implicated as a risk factor of PCOS, its pathological mechanism is still merely elucidated. Aiming to systematically explore the molecular basis of PCOS, we conducted a network analysis on gene expression profiles of ovary from PCOS women.Methods Ovarian gene expression profiles of PCOS women were collected by searching keywords of “PCOS and human” in GEO database.Then differentially expressed genes (DEGs) were identified by using Rankprod algorithm.Their primary functions were investigated by enrichment analysis based on KEGG and Gene Ontology.A core gene regulatory network in ovary of PCOS women was constructed as well, in which a significant role of the insulin signaling pathway in development of PCOS was highlighted.Result 269 up-regulated genes and 249 down-regulated ones (pfp < 0.05) were identified in ovary of PCOS patients.A PCOS ovarian gene regulatory network was constructed based on the above. By searching hub modules in this network, signaling process guided by two hub genes insulin receptor(INSR)and insulin receptor substrate 1(IRS1)was highlighted, which were elevated in PCOS subjects.Conclusions By integrating ovarian gene expression profiles, our network analysis revealed a significant role of insulin signaling pathway in Pathophysiology of PCOS. The elevated INSR and IRS1 would be a potential clue for insulin hypersensitivity in PCOS ovary, thereby inducing ovarian dysfunction by impairing the viability of granulosa cells.

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Section: Discussionmentioning

confidence: 99%

Network Analysis Suggests Ovarian Insulin Hypersensitivity Contributes to Depressed Viability of Ovarian Cells in PCOS Women

Wang,

Yang

et al. 2024

Preprint

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“…Diosgenin as a spirostanol saponin found in Trigonella foenum graecum (Fabaceae) showed prominent anti-cancer activities with different mechanisms, including downregulating PI3K/Akt/mTOR gene expression [ 136 ]. DG-8d, as a synthetic derivative of diosgenin, obstructed PI3K/Akt signaling pathway at 20 μM, thereby inhibiting the growth of non-small cell lung cancer cell lines [ 137 ]. In another study, A-24 (2–8 μM) as a spirostanol saponin of Allium chinense (Liliaceae) bulbs revealed anti-proliferation effects through blocking the PI3K/Akt/mTOR cellular signaling pathway on SGC-7901 and AGS, as human gastric adenocarcinoma cell lines [ 138 ].…”

Section: Saponinsmentioning

confidence: 99%

Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways

et al. 2023

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Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended.

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“…(120) DG-8d, bearing 1,3,4-oxadiazole/thiadiazole moieties, could down-regulate Bcl-2, PI3K, p-Akt and p-FOXO3a signal molecules, up-regulate Bax and Bim signal molecules, inhibit lung cancer cell proliferation and induce apoptosis by inhibiting PI3K/Akt signal pathway. (121) FZU-0021-194-P2 (P2) showed more potent cytotoxic activities against human NSCLC. (122) In addition, a fl uorophore-appended derivative of diosgenin [Glc/CNHphth-diosgenin (GND)] was synthesized, starting from diosgenin and glucosamine hydrochloride in overall yields.…”

Section: Drug Combinationmentioning

confidence: 99%

Anticancer Activity of Diosgenin and Its Molecular Mechanism

Ren

Wang

Zhang

et al. 2023

Chin. J. Integr. Med.

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Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea , and Rhizoma polgonati , has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro , and clinical studies reporting the diosgenin’s anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin’s deficiencies in clinical application. Electronic Supplementary Material Supplementary material is available in the online version of this article at 10.1007/s11655-023-3693-1.

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DG-8d, a novel diosgenin derivative, decreases the proliferation and induces the apoptosis of A549 cells by inhibiting the PI3k/Akt signaling pathway

Cited by 7 publications

References 36 publications

Network Analysis Suggests Ovarian Insulin Hypersensitivity Contributes to Depressed Viability of Ovarian Cells in PCOS Women

Network Analysis Suggests Ovarian Insulin Hypersensitivity Contributes to Depressed Viability of Ovarian Cells in PCOS Women

Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways

Anticancer Activity of Diosgenin and Its Molecular Mechanism

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