Gigantol attenuates the proliferation of human liver cancer HepG2 cells through the PI3K/Akt/NF-κB signaling pathway

Chen, Huanhuan; Huang, Yuechun; Huang, Junbin; Lin, Li-Ting; Wei, Gang

doi:10.3892/or.2016.5299

Cited by 45 publications

(48 citation statements)

References 32 publications

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“…Phenols derived from natural plants contain numerous antioxidants and therefore are typically used to study antioxidative activities (8)(9)(10)(11). Furthermore, gigantol is reported to exhibit numerous biological functions, including anti-osmosis effects (12), antitumor effects in human liver (13) and lung (14) cancer, antimutagenic effects (15) and immunomodulatory activities (16). Additionally, gigantol was reported to be a potent compound for restoring sight in diabetics with cataracts (17).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of gigantol against hydrogen peroxide‑induced apoptosis in rat bone marrow mesenchymal stem cells through the PI3K/Akt pathway

Chen

Huang

et al. 2017

Mol Med Report

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Bone marrow mesenchymal stem cell (BMSC) transplants are promising for the treatment of certain central nervous system diseases. However, oxidative stress is one of the major factors that may limit the survival of the transplanted BMSCs. The present study investigated the effect of pretreatment with gigantol on hydrogen peroxide (H2O2)‑induced apoptosis in rat BMSCs (rBMSCs) and the potential underlying mechanisms. The results demonstrated that gigantol pretreatment significantly inhibited H2O2‑induced apoptosis of rBMSCs. rBMSCs were incubated with 600 µM H2O2 in the absence or presence of different doses of gigantol (1‑100 µM). Cell viability and apoptosis ratios were assessed by MTT assays and flow cytometry, respectively. Morphological alterations and reactive oxygen species were measured by the fluorescent‑based methods of Hoechst staining and dichlorodihydrofluorescein diacetate, respectively. Furthermore, the protein levels of phosphorylated‑protein kinase B (Akt), B‑cell lymphoma‑2 (Bcl‑2), Bcl‑2‑associated X (Bax), caspase‑3 and caspase‑9 were investigated by western blotting. Following incubation with H2O2 for 2 h, gigantol significantly inhibited the H2O2‑induced reductions in the cell viability of rBMSCs in a dose‑dependent manner. Furthermore, gigantol upregulated Akt phosphorylation and Bcl‑2 expression, downregulated Bax expression, and reduced the expression of caspase‑3 and caspase‑9 in H2O2‑treated rBMSCs, whereas an opposite effect was detected when LY294002, an inhibitor of phosphatidylinositol 3‑kinase, was administered in combination with gigantol. These results indicate that gigantol may be developed as a promising neuroprotective agent for successful MSC transplantation in ischemic diseases.

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Section: Introductionmentioning

confidence: 99%

Protective effect of gigantol against hydrogen peroxide‑induced apoptosis in rat bone marrow mesenchymal stem cells through the PI3K/Akt pathway

Chen

Huang

et al. 2017

Mol Med Report

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“…In addition, phosphorylation of Akt, the downstream effector of PI3K, has been observed as a critical mediator in the NF-κβ signaling pathway promoting cell proliferation and protecting cancer cells against apoptosis in cancer cells [17]. Previous studies demonstrated that PI3K/Akt/NF-κβ signaling pathway was a crucial target in the mechanism investigation of therapeutic route in various cancer cells [18-20]. However, the detailed mechanisms of PI3K/Akt/NF-κβ signaling pathway and with the relationship to apoptosis of cancer are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

Jiang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteosarcoma, the most common primary bone malignancy, arises from primitive transformed cells of mesenchymal origin with the worldwide increasing morbidity and mortality. Previous studies found apoptosis of osteosarcoma cells was essential for an effective manner to improve the progress of osteosarcoma, and CXCR4 has been demonstrated to be relevant with various tumor progress and metastasis. Methods: The proliferation of cells transfected with CXCR4 shRNA and control shRNA were measured by BrdU assay. Apoptosis was detected by flow cytometry. Apoptotic protein expression levels were detected by Western blot. Caspase activity was detected by Colorimetric Assay Kits using microplate reader. Activation of NF-κβ signaling after CXCR4 down-regulation in osteosarcoma cells was examined by constructing NF-κβ promoter luciferase reporter plasmid. The expression and activation of NF-κβ Signaling relevant protein were analyzed to investigate the relationship between Akt and NF-κβ signaling after the down-regulation of CXCR4 in osteosarcoma cells. Results: Down-regulation of CXCR4 significantly reduced the cell proliferation, while remarkably increased the cell apoptosis and apoptotic protein expression levels in osteosarcoma cells. Furthermore, down-regulation of CXCR4 induced cell apoptosis was caspase dependent in osteosarcoma cells. This study also showed CXCR4 down-regulation induced apoptosis through inhibiting PI3K/Akt/NF-κβ signaling pathway. In addition, endoplasmic reticulum stress (ERS) activation was involved in cell apoptosis induced down-regulation of CXCR4. Knockdown of partial ERS relevant proteins followed down-regulation of CXCR4 significantly inhibited cell apoptosis and the apoptotic protein expression levels. Conclusions: Taken together, the results demonstrated that down-regulation of CXCR4 could induce apoptosis of human osteosarcoma cells through inhibiting PI3K/Akt/NF-κβ signaling pathway, indicating that CXCR4 could be vital for the clinical therapy of osteosarcoma.

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“…Previous studies have reported the potential anti-cancer activities of gigantol, one of the most widely studied bibenzyls. Gigantol has exhibited cytotoxicity against various types of cancer cells, such as breast, liver, and lung cancer cells [24,32,33]. Moreover, gigantol could attenuate certain aggressive phenotypes that bring about tumor progression and metastasis, including proliferation, migration, invasion, anoikis-resistance, and anchorage-independent growth [25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Gigantol Targets Cancer Stem Cells and Destabilizes Tumors via the Suppression of the PI3K/AKT and JAK/STAT Pathways in Ectopic Lung Cancer Xenografts

Losuwannarak

Maiuthed

Kitkumthorn

et al. 2019

Cancers

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Lung cancer has long been recognized as an important world heath concern due to its high incidence and death rate. The failure of treatment strategies, as well as the regrowth of the disease driven by cancer stem cells (CSCs) residing in the tumor, lead to the urgent need for a novel CSC-targeting therapy. Here, we utilized proteome alteration analysis and ectopic tumor xenografts to gain insight on how gigantol, a bibenzyl compound from orchid species, could attenuate CSCs and reduce tumor integrity. The proteomics revealed that gigantol affected several functional proteins influencing the properties of CSCs, especially cell proliferation and survival. Importantly, the PI3K/AKT/mTOR and JAK/STAT related pathways were found to be suppressed by gigantol, while the JNK signal was enhanced. The in vivo nude mice model confirmed that pretreatment of the cells with gigantol prior to a tumor becoming established could decrease the cell division and tumor maintenance. The results indicated that gigantol decreased the relative tumor weight with dramatically reduced tumor cell proliferation, as indicated by Ki-67 labeling. Although gigantol only slightly altered the epithelial-to-mesenchymal and angiogenesis statuses, the gigantol-treated group showed a dramatic loss of tumor integrity as compared with the well-grown tumor mass of the untreated control. This study reveals the effects of gigantol on tumor initiation, growth, and maintain in the scope that the cells at the first step of tumor initiation have lesser CSC property than the control untreated cells. This study reveals novel insights into the anti-tumor mechanisms of gigantol focused on CSC targeting and destabilizing tumor integrity via suppression of the PI3K/AKT/mTOR and JAK/STAT pathways. This data supports the potential of gigantol to be further developed as a drug for lung cancer.

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Gigantol attenuates the proliferation of human liver cancer HepG2 cells through the PI3K/Akt/NF-κB signaling pathway

Cited by 45 publications

References 32 publications

Protective effect of gigantol against hydrogen peroxide‑induced apoptosis in rat bone marrow mesenchymal stem cells through the PI3K/Akt pathway

Protective effect of gigantol against hydrogen peroxide‑induced apoptosis in rat bone marrow mesenchymal stem cells through the PI3K/Akt pathway

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

Gigantol Targets Cancer Stem Cells and Destabilizes Tumors via the Suppression of the PI3K/AKT and JAK/STAT Pathways in Ectopic Lung Cancer Xenografts

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