Inactivation of PI3K/Akt signaling mediates proliferation inhibition and G2/M phase arrest induced by andrographolide in human glioblastoma cells

Li, Yanchun; Zhang, Pengfei; Qiu, Feng; Chen, Lixia; Miao, Caixia; Li, Jianchun; Xiao, Wei; Ma, Enlong

doi:10.1016/j.lfs.2012.04.044

Cited by 56 publications

(41 citation statements)

References 30 publications

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“…While the pathways that lead to apoptosis can be established, the pathway leading to cell cycle arrest is less clear. The present study is consistent with several others in demonstrating down regulation of the Akt/mTOR survival pathway [15, 30–32]. Blocking this pathway can contribute to cell cycle arrest.…”

Section: Discussionsupporting

confidence: 93%

Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells

Banerjee

Czinn

et al. 2017

Oncotarget

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Chemotherapy continues to play an essential role in the management of many cancers including colon cancer, the third leading cause of death due to cancer in the United States. Many naturally occurring plant compounds have been demonstrated to possess anti-cancer cell activity and have the potential to supplement existing chemotherapy strategies. The plant metabolite andrographolide induces cell death in cancer cells and apoptosis is dependent upon the induction of endoplasmic reticulum stress (ER stress) leading to the unfolded protein response (UPR). The goal of the present study was to determine the mechanism by which andrographolide induces ER stress and to further evaluate its role in promoting cell death pathways. The T84 and COLO 205 cancer cell lines were used to demonstrate that andrographolide induces increased ROS levels, corresponding anti-oxidant response molecules, and reduced mitochondrial membrane potential. No increases in ROS levels were detected in control colon fibroblast cells. Andrographolide-induced cell death, UPR signaling, and CHOP, Bax, and caspase 3 apoptosis elements were all inhibited in the presence of the ROS scavenger NAC. Additionally, andrographolide-induced suppression of cyclins B1 and D1 were also reversed in the presence of NAC. Finally, Akt phosphorylation and phospho-mTOR levels that are normally suppressed by andrographolide were also expressed at normal levels in the absence of ROS. These data demonstrate that andrographolide induces ER stress leading to apoptosis through the induction of ROS and that elevated ROS also play an important role in down-regulating cell cycle progression and cell survival pathways as well.

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Section: Discussionsupporting

confidence: 93%

Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells

Banerjee

Czinn

et al. 2017

Oncotarget

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“…31 Similar findings have been reported by others using human glioblastoma cells. 32 Since anaphase-promoting complex degrades cyclin B1 before cell cycle proceeds, increased levels of cyclin B1 observed in LNCaP and PC3 cells, may be due to a halt at 'pre' anaphase stage of mitosis. Thus AG affects cell cycle in LNCaP and C4-2b cells mainly via cyclin A2 and B1 whereas in DU-145 cells cyclin E related regulation is more important.…”

Section: Discussionmentioning

confidence: 99%

Andrographolide inhibits prostate cancer by targeting cell cycle regulators, CXCR3 and CXCR7 chemokine receptors

et al. 2016

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Despite state of the art cancer diagnostics and therapies offered in clinic, prostate cancer (PCa) remains the second leading cause of cancer-related deaths. Hence, more robust therapeutic/preventive regimes are required to combat this lethal disease. In the current study, we have tested the efficacy of Andrographolide (AG), a bioactive diterpenoid isolated from Andrographis paniculata, against PCa. This natural agent selectively affects PCa cell viability in a dose and time-dependent manner, without affecting primary prostate epithelial cells. Furthermore, AG showed differential effect on cell cycle phases in LNCaP, C4-2b and PC3 cells compared to retinoblastoma protein (RB ¡/¡ ) and CDKN2A lacking DU-145 cells. G2/M transition was blocked in LNCaP, C4-2b and PC3 after AG treatment whereas DU-145 cells failed to transit G1/S phase. This difference was primarily due to differential activation of cell cycle regulators in these cell lines. Levels of cyclin A2 after AG treatment increased in all PCa cells line. Cyclin B1 levels increased in LNCaP and PC3, decreased in C4-2b and showed no difference in DU-145 cells after AG treatment. AG decreased cyclin E2 levels only in PC3 and DU-145 cells. It also altered Rb, H3, Wee1 and CDC2 phosphorylation in PCa cells. Intriguingly, AG reduced cell viability and the ability of PCa cells to migrate via modulating CXCL11 and CXCR3 and CXCR7 expression. The significant impact of AG on cellular and molecular processes involved in PCa progression suggests its potential use as a therapeutic and/or preventive agent for PCa.

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“…In B16F-10 melanoma cells, AND modulated p53-induced-caspase-3 expression [24]. A recent study demonstrated that AND inhibited cell proliferation via inactivation of PI3K/AKT signaling in human glioblastoma cells [25]. Beside, AND also sensitizes cancer cells to TRAIL-induced apoptosis via p53 [26].…”

Section: Introductionmentioning

confidence: 99%

Andrographolide Induces Apoptosis of C6 Glioma Cells via the ERK-p53-Caspase 7-PARP Pathway

Yang

Wang

Syu

et al. 2014

BioMed Research International

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Background. Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND), a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo. Methods. Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model. Results and Conclusion. In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway. In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.

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Inactivation of PI3K/Akt signaling mediates proliferation inhibition and G2/M phase arrest induced by andrographolide in human glioblastoma cells

Cited by 56 publications

References 30 publications

Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells

Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells

Andrographolide inhibits prostate cancer by targeting cell cycle regulators, CXCR3 and CXCR7 chemokine receptors

Andrographolide Induces Apoptosis of C6 Glioma Cells via the ERK-p53-Caspase 7-PARP Pathway

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