JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from <i>Gymnanthemum extensum</i> on A549 human lung carcinoma cells

Keeratichamroen, Siriporn; Lirdprapamongkol, Kriengsak; Thongnest, Sanit; Boonsombat, Jutatip; Chawengrum, Pornsuda; Sornprachum, Thiwaree; Sirirak, Jitnapa; Verathamjamras, Chris; Ornnork, Narittira; Ruchirawat, Somsak; Svasti, Jisnuson

doi:10.3892/or.2021.8217

Cited by 8 publications

(8 citation statements)

References 47 publications

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“…[22] Additionally, treatment with STAT3-specific inhibitor, cucurbitacin-I, at a lethal concentration resulted in Mcl-1 downregulation in A549 cells. [23] Accordingly, this evidence could confirm the association between STAT3 inhibition and downregulation of Bcl-2 and Mcl-1 in A549 cells treated with PCNT13, PCNT13b, and PCNT13c observed in this study.…”

Section: Suppressive Effects Of the Pcnt13 Series On Antiapoptotic Pr...supporting

confidence: 86%

“…Briefly, A549 cells (1×10 5 cells) were seeded in a 6‐well plate one day before treatment with test compounds at desired concentrations for 24 h. Images of treated cells were taken at original magnification ×200. The treated cells were harvested by trypsinization and prepared for cell cycle analysis as described previously [23] . The results were expressed as percentages of cell populations in G0/G1, S, and G2/M phases.…”

Section: Methodsmentioning

confidence: 99%

“…The treated cells were harvested by trypsinization and prepared for cell cycle analysis ChemMedChem as described previously. [23] The results were expressed as percentages of cell populations in G0/G1, S, and G2/M phases.…”

Section: Cell Cycle Analysismentioning

confidence: 99%

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Biphasic Dose‐Dependent G0/G1 and G2/M Cell‐Cycle Arrest by Synthetic 2,3‐Arylpyridylindole Derivatives in A549 Lung Cancer Cells

et al. 2022

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A collection of 2,3‐arylpyridylindole derivatives were synthesized via the Larock heteroannulation and evaluated for their in vitro cytotoxic activity against A549 human lung cancer cells. Two derivatives expressed good cytotoxicity with IC50 values of 1.18±0.25 μM and 0.87±0.10 μM and inhibited tubulin polymerization in vitro, with molecular docking studies suggesting the binding modes of the compounds in the colchicine binding site. Both derivatives have biphasic cell cycle arrest effects depending on their concentrations. At a lower concentration (0.5 μM), the two compounds induced G0/G1 cell cycle arrest by activating the JNK/p53/p21 pathway. At a higher concentration (2.0 μM), the two derivatives arrested the cell cycle at the G2/M phase via Akt signaling and inhibition of tubulin polymerization. Additional cytotoxic mechanisms of the two compounds involved the decreased expression of Bcl‐2 and Mcl‐1 antiapoptotic proteins through inhibition of the STAT3 and Akt signaling pathways.

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Section: Suppressive Effects Of the Pcnt13 Series On Antiapoptotic Pr...supporting

confidence: 86%

Section: Methodsmentioning

confidence: 99%

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Biphasic Dose‐Dependent G0/G1 and G2/M Cell‐Cycle Arrest by Synthetic 2,3‐Arylpyridylindole Derivatives in A549 Lung Cancer Cells

et al. 2022

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“…The apoptotic profiles and cell cycle progression of A549 cells cultured in 2D/3D culturing microenvironments were assessed using Muse ® Cell Analyzer (Luminex) as previously described (21). Briefly, the cells were harvested, dissociated into single-cell suspensions and stained with Muse Annexin V & Dead Cell kit or Muse Cell Cycle kit (Luminex), according to the manufacturer's instructions.…”

Section: Flow Cytometric Analysis Of Apoptosis and Cell Cycle Distrib...mentioning

confidence: 99%

p‑STAT3 influences doxorubicin and etoposide resistance of A549 cells grown in an in vitro 3D culture model

et al. 2023

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Tumor microenvironment undoubtedly has a significant impact on therapeutic responses. Abundant evidence suggests that the 3D in vitro culture holds great promise for drug discovery and development by bridging the gap between conventional 2D culture and animal models. The present study described 3D basement membrane culture of A549 cells, which mimics the complex 3D arrangement of tumors in vivo and elucidates the underlying mechanisms of microenvironmental influences on cellular functions and therapeutic efficacy. A549 cells cultured in 3D undergo G 0 /G 1 phase arrest and decreased migratory and invasive capacity, indicating dormant cell characteristics. Hypoxia, apoptosis and stemness were demonstrated in the A549 cells in 3D architecture compared with the 2D-cultured counterparts. More importantly, cells in the 3D environment exhibited increased resistance to different classes of anticancer agents. Western blotting revealed changes in the levels of key cancer-associated pathways, phosphorylated (p)-STAT3, p-ERK, and p-Akt, in response to 3D culture compared with 2D monolayer culture. Notably, mechanistic analysis using specific inhibitors showed that the STAT3 inhibitor overcomes the 3D culture-induced doxorubicin and etoposide resistance. These results implicated an important role of p-STAT3 in conferring chemoresistance in 3D-cultured A549 cells, as well as the use of STAT3 inhibitor as a potential chemosensitizer to improve drug sensitivity. Thus, 3D culture systems, that more closely resemble in vivo tumor biology, may be more effective models in searching for novel chemotherapeutic agents and therapeutic targets for cancer treatment.

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“…Previously classified as a plant of the genus Vernonia and called Vernonia theophrastifolia , V. myriocephala , V. seretii , V. macrophylla , or V. richardiana , G. theophrastifolium , having the basionym Cacalia richardiana Kuntze, has been reclassified since 2008 by Lebrun and Stork under the genus Gymnanthemun [5] . One of the rare research works carried out on one species of the genus, namely G. extensum , revealed the occurrences of elemane‐type sesquiterpenoids [6] . However, phytochemical screening of extracts from G. coloratum revealed the presence of alkaloids, anthocyanins, cardenolids, coumarins, flavonoids, glycosides, leucoanthocyanins, and terpenoids amongst others [7] .…”

Section: Introductionmentioning

confidence: 99%

Elemane‐Type Sesquiterpene, Acetonide Derived Polyacetylene and Other Constituents from the Whole Plant of Gymnanthemum theophrastifolium (Schweinf. ex Oliv. & Hiern) H.Rob. and Their Chemophenetic Significance

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Ndontsa

Nono

et al. 2023

Chemistry & Biodiversity

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The chemical investigation of the methanol extract of the whole plant of Gymnanthemum theophrastifolium (Schweinf. ex Oliv. & Hiern) H.Rob. (Asteraceae) led to the isolation of a new elemane-type sesquiterpene (1), a new acetonide derived polyacetylene (2) and a naturally occurring compound (3) from the plant kingdom along with sixteen known compounds (4 -19). Their structures were elucidated by extensive NMR and MS analysis. This is the first report on the chemical constituents of G. theophrastifolium. Furthermore, compounds 12, 13, and 14 are reported for the first time from the family Asteraceae, while compound 9 is reported for the first time from the genus Gymnanthemum. Thus, the present results provide valuable insights to the chemophenetic knowledge of G. theophrastifolium, which is also discussed in this work.

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JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones from Gymnanthemum extensum on A549 human lung carcinoma cells

Cited by 8 publications

References 47 publications

Biphasic Dose‐Dependent G0/G1 and G2/M Cell‐Cycle Arrest by Synthetic 2,3‐Arylpyridylindole Derivatives in A549 Lung Cancer Cells

Biphasic Dose‐Dependent G0/G1 and G2/M Cell‐Cycle Arrest by Synthetic 2,3‐Arylpyridylindole Derivatives in A549 Lung Cancer Cells

p‑STAT3 influences doxorubicin and etoposide resistance of A549 cells grown in an in vitro 3D culture model

Elemane‐Type Sesquiterpene, Acetonide Derived Polyacetylene and Other Constituents from the Whole Plant of Gymnanthemum theophrastifolium (Schweinf. ex Oliv. & Hiern) H.Rob. and Their Chemophenetic Significance

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