JNK pathway and relative transcriptional factor were involved in ginsenoside Rh2-mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells

Liu, X.; Sun, Yunpeng; Yue, Liling; Li, S.; Qi, Xiao; Zhao, Hong; Yang, Ying; Zhang, C.; Yu, Haitao

doi:10.4238/gmr.15039003

Cited by 21 publications

(8 citation statements)

References 33 publications

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“…The results revealed that GRh2 impaired HeLa cell proliferation in a doseand time-dependent manner. These findings are in accordance with previous reports that demonstrated that ginseng Rh2 prevents cell proliferation in colon, lung, liver, and gastric cancers, in addition to leukemia and glioblastoma (38)(39)(40)(41)(42). In addition, it was observed that GRh2 inhibited the activation of the Akt pathway in HeLa cells.…”

Section: Discussionsupporting

confidence: 93%

Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through the Akt/GSK3β signaling pathway in human cervical cancer cells

2018

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Ginsenoside 20(S)-Rh2 (GRh2) is a bioactive compound derived from ginseng that is believed to maintain health in traditional Chinese medicine. Emerging evidence has suggested that GRh2 exhibits anti‑cancer activity. The present study hypothesized that GRh2 has an anti‑cancer function in human cervical cancer cells. An MTS assay demonstrated that GRh2 attenuated proliferation of HeLa cells in a dose‑ and time‑dependent manner. In addition, GRh2 inhibited migration and invasion, as determined by wound healing and transwell invasion assays, respectively. Furthermore, GRh2 treatment reduced expression of mesenchymal markers N‑cadherin and vimentin as well as epithelial mesenchymal transition transcriptional factor zinc finger E‑box‑binding homeobox 1 and snail1, and increased the protein expression levels of epithelial marker E‑cadherin. In addition, the results revealed that GRh2 prevented activation of the protein kinase B (Akt)/glycogen synthase kinase (GSK)3β signaling pathway in HeLa cells. In conclusion, the results suggested that GRh2 inhibits cervical cancer cell proliferation by targeting the Akt pathway, and prevents cervical cancer cell migration and invasion by suppressing the Akt/GSK3β regulated EMT process, and therefore, GRh2 may have the potential to be a novel anti‑cancer agent for cervical cancer.

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Section: Discussionsupporting

confidence: 93%

Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through the Akt/GSK3β signaling pathway in human cervical cancer cells

2018

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“…The results demonstrated that G-Rh2 decreased the expression of Bcl-2 and increased the expression of Bax, caspase-3 and Smad4 in LoVo/L-OHP and LoVo cells. As reported previously, G-Rh2 inhibits tumor cell growth and prevents cells from entering the growth phase, including the G2/M, G1/S and S phases, respectively (25,26). G-Rh2 can inhibit A172 human glioma cell proliferation and induce cell cycle arrest status (27).…”

Section: Discussionsupporting

confidence: 61%

“…A previous study reported that G-Rh2 induces apoptosis via the activation of caspase-1 and −3 and upregulation of Bax in human neuroblastoma (17). G-Rh2 can inhibit the proliferation of the A549 human lung adenocarcinoma cell line in a dose-dependent manner by activating caspase-8/3 to promote apoptosis (25). In the present study, the effects of G-Rh2 on cell apoptosis-related molecules were investigated.…”

Section: Discussionmentioning

confidence: 99%

Reversal effect of ginsenoside Rh2 on oxaliplatin‑resistant colon cancer cells and its mechanism

Gao

et al. 2019

Exp Ther Med

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Chemotherapy is an important treatment modality for colon cancer, however, drug resistance is the main factor leading to treatment failure. Ginsenoside Rh2 (G-Rh2), the main bioactive metabolite of ginseng, is known to possess the ability to potently induce cell apoptosis, inhibit cell proliferation and reverse multidrug resistance in a variety of cancer cells. The present study examined the effect of G-Rh2 on oxaliplatin (L-OHP)-resistant colon cancer cells and its potential mechanism. L-OHP-resistant colon cancer cells (LoVo/L-OHP) and LoVo cells were used in the present study. The effect of G-Rh2 on LoVo/L-OHP and LoVo cell proliferation was measured using a 3-(4,5 dimethylthiazol-z-yl)-3,5-diphenyltetrazolium bromide assay. The effects of G-Rh2 on LoVo/L-OHP and LoVo cell apoptosis were detected by flow cytometry. The mRNA and protein expression of apoptosis-related genes Bax, Bcl-2 and caspase-3, drug resistance-related genes P-glycoprotein (P-gp) and Smad4, were determined in LoVo/L-OHP and LoVo cells treated with G-Rh2 by reverse transcription-quantitative polymerase chain reaction and western blot analyses. G-Rh2 treatment significantly inhibited the proliferation and induced the apoptosis of LoVo/L-OHP and LoVo cells. In addition, G-Rh2 treatment resulted in a significant increase in pro-apoptotic factors, Bax and caspase-3, and decrease in anti-apoptotic factor Bcl-2 in the LoVo/L-OHP and LoVo cells. Furthermore, G-Rh2 treatment significantly decreased the levels of P-gp and increased the levels of Smad4 in the LoVo/L-OHP and LoVo cells. It was found that L-OHP had no significant effects on LoVo/L-OHP cell proliferation or apoptosis, whereas G-Rh2 + L-OHP treatment significantly inhibited LoVo/L-OHP cell proliferation and induced apoptosis. L-OHP had no significant effects on the expression of P-gp, Smad4, Bcl-2, Bax or caspase-3 in LoVo/L-OHP cells. Treatment with G-Rh2 + L-OHP significantly reduced the expression of P-gp and Bcl-2, and enhanced the expression levels of Smad4, Bax and caspase-3. These findings demonstrated that G-Rh2 reversed the drug resistance of LoVo/L-OHP cells to L-OHP, and this may be mediated by inhibiting cell proliferation and promoting apoptosis and regulating the expression of drug resistance genes. These results suggest that G-Rh2 may function as a potent anticancer drug for drug resistance in colon cancer treatment.

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“…Members of the MAP kinase cascade such as JNK and p38 could be activated by PAKs 1-3 in related study [26]. Moreover, JNK and p38 signaling pathway are considered as critical signal transduction pathways involved in cell proliferation, cell cycle arrest, and apoptosis [27]. Besides, PAK has been shown to protect apoptotic signals by promoting translocation of Raf-1 to the mitochondria, triggering formation of Raf-1-Bcl-2 complexes, and depressing the formation of BAD-Bcl-2 complexes [28].…”

Section: Discussionmentioning

confidence: 93%

MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancer

Guo

et al. 2019

FEBS Open Bio

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MicroRNAs (miR) are known to be critical regulators in tumor progression. miR‐7‐5p was reported to be involved in several cancers, including glioblastoma, cervical cancer, and melanoma, but its prognostic value and biological function in non‐small‐cell lung cancer (NSCLC) remain unclear. In this study, using quantitative real‐time PCR analysis, we found that miR‐7‐5p was significantly downregulated in NSCLC tissues and cell lines. Lower miR‐7‐5p expression was associated with tumor–node–metastasis stage and tumor size by chi‐squared test. Deceased miR‐7‐5p expression was associated with a worse prognosis in patients with NSCLC using Kaplan–Meier survival analysis and multivariate Cox regression analysis. Experiments in NSCLC cell lines (A549 and H1299) demonstrated that upregulation of miR‐7‐5p significantly suppressed cell proliferation, but induced cell cycle G0/G1 phase arrest and apoptosis using Cell Counting Kit‐8, colony formation, and flow cytometry analysis. Through loss‐of‐function assays, we further demonstrated that downregulation of miR‐7‐5p promoted cell proliferation and cell cycle G1/S transition, but decreased cell apoptosis in SPC‐A1 cells. Furthermore, P21‐activated kinase 2 (PAK2) was predicted and confirmed as a direct target gene of miR‐7‐5p in NSCLC cells by luciferase reporter assay. In addition, we found PAK2 overexpression could partially reverse the effects of miR‐7‐5p on cell proliferation, cell cycle distribution, and apoptosis. We thus concluded that lower expression of miR‐7‐5p was associated with poor prognosis and NSCLC progression by directly targeting PAK2.

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JNK pathway and relative transcriptional factor were involved in ginsenoside Rh2-mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells

Cited by 21 publications

References 33 publications

Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through the Akt/GSK3β signaling pathway in human cervical cancer cells

Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through the Akt/GSK3β signaling pathway in human cervical cancer cells

Reversal effect of ginsenoside Rh2 on oxaliplatin‑resistant colon cancer cells and its mechanism

MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancer

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