Apigetrin induces extrinsic apoptosis, autophagy and G2/M phase cell cycle arrest through PI3K/AKT/mTOR pathway in AGS human gastric cancer cell

Kim, Sang Woo; Vetrivel, Preethi; Ha, Sang Eun; Kim, Hun Hwan; Kim, Jina

doi:10.1016/j.jnutbio.2020.108427

Cited by 59 publications

(42 citation statements)

References 48 publications

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“…Inhibition of CyclinB1, CDK1, and Cdc25C cell cycle proteins causes arrest in the G2/M phase. Previous studies also showed that flavonoids such as scutellarein and apigetrin induced G2/M phase cell cycle arrest and apoptosis in Hep3B and AGS cells, respectively [ 13 , 34 ].…”

Section: Discussionmentioning

confidence: 97%

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Iridin Induces G2/M Phase Cell Cycle Arrest and Extrinsic Apoptotic Cell Death through PI3K/AKT Signaling Pathway in AGS Gastric Cancer Cells

Bhosale

Vetrivel

et al. 2021

Molecules

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Iridin is a natural flavonoid found in Belamcanda chinensis documented for its broad spectrum of biological activities like antioxidant, antitumor, and antiproliferative effects. In the present study, we have investigated the antitumor potential of iridin in AGS gastric cancer cells. Iridin treatment decreases AGS cell growth and promotes G2/M phase cell cycle arrest by attenuating the expression of Cdc25C, CDK1, and Cyclin B1 proteins. Iridin-treatment also triggered apoptotic cell death in AGS cells, which was verified by cleaved Caspase-3 (Cl- Caspase-3) and poly ADP-ribose polymerase (PARP) protein expression. Further apoptotic cell death was confirmed by increased apoptotic cell death fraction shown in allophycocyanin (APC)/Annexin V and propidium iodide staining. Iridin also increased the expression of extrinsic apoptotic pathway proteins like Fas, FasL, and cleaved Caspase-8 in AGS cells. On the contrary, iridin-treated AGS cells did not show variations in proteins related to an intrinsic apoptotic pathway such as Bax and Bcl-xL. Besides, Iridin showed inhibition of PI3K/AKT signaling pathways by downregulation of (p-PI3K, p-AKT) proteins in AGS cells. In conclusion, these data suggest that iridin has anticancer potential by inhibiting PI3K/AKT pathway. It could be a basis for further drug design in gastric cancer treatment.

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Section: Discussionmentioning

confidence: 97%

“…PI3K/AKT signaling pathway is one of the essential intracellular pathways that regulate survival, cell growth, differentiation, and cellular metabolism [ 13 , 14 ]. The components of this pathway are often irregular in a variety of tumors, making it a preferred candidate for anticancer therapy [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Iridin Induces G2/M Phase Cell Cycle Arrest and Extrinsic Apoptotic Cell Death through PI3K/AKT Signaling Pathway in AGS Gastric Cancer Cells

Bhosale

Vetrivel

et al. 2021

Molecules

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“…Accumulating evidence suggests that the PI3K‐AKT signalling pathway is involved in the pathogenesis of GC and regulates cellular processes, such as differentiation, proliferation and metastasis 37‐39 . Moreover, inhibition of the PI3K‐AKT signalling pathway can block the cell cycle in GC cell lines 40 . Therefore, we focussed on the PI3K‐AKT pathway.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of CENPK inhibits cell growth and facilitates apoptosis via PTEN‐PI3K‐AKT signalling pathway in gastric cancer

Cao

et al. 2021

J Cellular Molecular Medi

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Previous studies have indicated that centromere protein K (CENPK) is upregulated in several cancers and related to tumorigenesis. Nevertheless, the potential function of CENPK in gastric cancer (GC) remains unknown. Here, we investigated the function of CENPK on oncogenicity and explored its underlying mechanisms in GC. Our results showed that CENPK was dramatically overexpressed in GC and was associated with poor prognosis through bioinformatics analysis. We demonstrated that CENPK is upregulated in GC tissues and cell lines. Moreover, knockdown of CENPK significantly inhibited proliferation in vitro and attenuated the growth of implanted GCs in vivo. In addition, CENPK silencing induced G1 phase cell cycle arrest and facilitated apoptosis of GC cells. KEGG pathway analysis indicated that the PI3K‐AKT signalling pathway was considerably enriched. Knockdown of CENPK decreased the expression of PI3K, p‐Akt (Ser437) and p‐GSK3β (Ser9) in GC cells, and increased the expression of PTEN. In conclusion, this study indicated that CENPK was overexpressed in GC and may promote gastric carcinogenesis through the PTEN‐PI3K‐AKT signalling pathway. Thus, CENPK may be a potential target for cancer therapeutics in GC.

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“…The Western blot analysis was performed as described before (43). After 48 h treatment of each compounds, the cells were lysed with RIPA buffer (50 mM Tris-HCl pH 7.5, 0.1% SDS, 1% Triton X-100, 150 mM NaCl, 0.5% Sodium deoxycholate, and 2 mM EDTA) containing protease/phosphatase inhibitor cocktail (Thermo Fisher Scientific, Waltham, MA, USA) at 4°C for 1 h. The supernatants were collected and quantified using BCA protein assay kit (Thermo Fisher Scientific) according to the manufacturer's instructions.…”

Section: Western Blot Analysismentioning

confidence: 99%

Novel Butein Derivatives Repress DDX3 Expression by Inhibiting PI3K/AKT Signaling Pathway in MCF-7 and MDA-MB-231 Cell Lines

et al. 2021

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BackgroundBreast cancer is one of the major causes of mortalities noticed in women globally. DDX3 has emerged as a potent target for several cancers, including breast cancer to which currently there are no reported or approved drugs.MethodsTo find effective cancer therapeutics, three compounds were computationally designed tweaking the structure of natural compound butein. These compounds were synthesized and evaluated for their anticancer property in MCF-7 and MDA-MB-231 cell lines targeting DDX3. The in silico molecular docking studies have shown that the compounds have occupied the binding site of the human DDX3 target. Furthermore, to investigate the cell viability effect of 3a, 3b, and 3c on MCF-7 and MDA-MB-231 cell lines, the cell lines were treated with different concentrations of compounds for 24 and 48 h and measured using MTT assay.ResultsThe cell viability results showed that the have induced dose dependent suppression of DDX3 expression. Additionally, 3b and 3c have reduced the expression of DDX3 in MCF-7 and MDA-MD-231 cell lines. 3b or 3c treated cell lines increased apoptotic protein expression. Both the compounds have induced the apoptotic cell death by elevated levels of cleaved PARP and cleaved caspase 3 and repression of the anti-apoptosis protein BCL-xL. Additionally, they have demonstrated the G2/M phase cell cycle arrest in both the cell lines. Additionally, 3c decreased PI3K and AKT levels.ConclusionsOur results shed light on the anticancer ability of the designed compounds. These compounds can be employed as chemical spaces to design new prospective drug candidates. Additionally, our computational method can be adapted to design new chemical scaffolds as plausible inhibitors.

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Apigetrin induces extrinsic apoptosis, autophagy and G2/M phase cell cycle arrest through PI3K/AKT/mTOR pathway in AGS human gastric cancer cell

Cited by 59 publications

References 48 publications

Iridin Induces G2/M Phase Cell Cycle Arrest and Extrinsic Apoptotic Cell Death through PI3K/AKT Signaling Pathway in AGS Gastric Cancer Cells

Iridin Induces G2/M Phase Cell Cycle Arrest and Extrinsic Apoptotic Cell Death through PI3K/AKT Signaling Pathway in AGS Gastric Cancer Cells

Knockdown of CENPK inhibits cell growth and facilitates apoptosis via PTEN‐PI3K‐AKT signalling pathway in gastric cancer

Novel Butein Derivatives Repress DDX3 Expression by Inhibiting PI3K/AKT Signaling Pathway in MCF-7 and MDA-MB-231 Cell Lines

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