Targeted disruption of PI3K/Akt/mTOR signaling pathway, via PI3K inhibitors, promotes growth inhibitory effects in oral cancer cells

Aggarwal, Sadhna; John, Sarah; Sapra, Leena; Sharma, Suresh C.; Das, Satya

doi:10.1007/s00280-018-3746-x

Cited by 48 publications

(37 citation statements)

References 47 publications

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“…Extracellular signal-regulated kinase (ERK) controls many aspects of cell physiology including cell apoptosis [21]. AKT is a known regulator of autophagy [22] and the AKT/mTOR pathway is one of the major signaling pathways involved in autophagy [23]. Here, we further showed signaling pathways of ERK, AKT, mTOR and their phosphorylation in GCs of different size follicles.…”

Section: Discussionmentioning

confidence: 71%

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

Zheng

Liu

et al. 2019

Animals

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Follicular atresia is closely related to both apoptosis and autophagy of granulosa cells (GCs) in ovarian follicles. In the present study, GCs were isolated from pig ovaries in small, medium and large antral follicles, and the current results showed that the proliferation of GCs was higher in medium follicles, and lower in large follicles compared to small follicles. The Bax and Caspase 3 mRNA levels were significantly higher, but the ratio of Bcl-2/Bax was lower in GCs of large follicles. The marker genes of autophagy, Atg3, Atg7 and LC3 mRNA levels were higher in GCs from medium follicles. Apoptosis- and autophagy-related proteins had a similar expression pattern to the mRNA level. Our results showed that phosphorylated ERK (p-ERK) was activated in GCs of large follicles, while phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) were inhibited in GCs of medium follicles. Labeling of autophagic vesicles with 4’,6-diamidino-2-phenylindole (DAPI) and monodansylcadaverine (MDC) confirmed the results of gene transcription and protein expression in GCs of different size follicles. We conclude that autophagy and apoptosis of GCs occurred in different size follicles during follicular development, and autophagy was mainly found in GCs of medium follicles, while apoptosis was mainly found in GCs of large follicles.

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Section: Discussionmentioning

confidence: 71%

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

Zheng

Liu

et al. 2019

Animals

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“…The mammalian target of rapamycin (mTOR) signaling pathway is important for cell growth, leading to the facilitation of cancer progression [24,25]. Ribosomal protein S6 kinase (p70S6K) is a well-known modulator for the translational pathway that generally dominates cell death or survival.…”

Section: Zno-nps Inhibited P70s6k Signaling Pathway In Gingival Squammentioning

confidence: 99%

ZnO Nanoparticles Induced Caspase-Dependent Apoptosis in Gingival Squamous Cell Carcinoma through Mitochondrial Dysfunction and p70S6K Signaling Pathway

Wang

Lee

Lin

et al. 2020

IJMS

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Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, food additives, pigments, rubber manufacture, and electronic materials. Several studies have shown that ZnO-NPs inhibit cell growth and induce apoptosis by the production of oxidative stress in a variety of human cancer cells. However, the anti-cancer property and molecular mechanism of ZnO-NPs in human gingival squamous cell carcinoma (GSCC) are not fully understood. In this study, we found that ZnO-NPs induced growth inhibition of GSCC (Ca9-22 and OECM-1 cells), but no damage in human normal keratinocytes (HaCaT cells) and gingival fibroblasts (HGF-1 cells). ZnO-NPs caused apoptotic cell death of GSCC in a concentration-dependent manner by the quantitative assessment of oligonucleosomal DNA fragmentation. Flow cytometric analysis of cell cycle progression revealed that sub-G1 phase accumulation was dramatically induced by ZnO-NPs. In addition, ZnO-NPs increased the intracellular reactive oxygen species and specifically superoxide levels, and also decreased the mitochondrial membrane potential. ZnO-NPs further activated apoptotic cell death via the caspase cascades. Importantly, anti-oxidant and caspase inhibitor clearly prevented ZnO-NP-induced cell death, indicating the fact that superoxide-induced mitochondrial dysfunction is associated with the ZnO-NP-mediated caspase-dependent apoptosis in human GSCC. Moreover, ZnO-NPs significantly inhibited the phosphorylation of ribosomal protein S6 kinase (p70S6K kinase). In a corollary in vivo study, our results demonstrated that ZnO-NPs possessed an anti-cancer effect in a zebrafish xenograft model. Collectively, these results suggest that ZnO-NPs induce apoptosis through the mitochondrial oxidative damage and p70S6K signaling pathway in human GSCC. The present study may provide an experimental basis for ZnO-NPs to be considered as a promising novel anti-tumor agent for the treatment of gingival cancer.

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“…[14][15][16] There is evidence that PI3K/ Akt signaling pathway participates in the modulation of intracellular autophagy. [17][18][19] Inhibition of PI3K/Akt signaling transduction by regulating autophagy facilitates the enhancement of the radiosensitivity of prostate cancer, glioma, and so forth. [20][21][22] These reports indicate that PI3K/ Akt signaling pathway is a key switch in the course of autophagy-mediated radiosensitivity.…”

Section: Introductionmentioning

confidence: 99%

Effect of combination of curcumin and GLUT‐1 AS‐ODN on radiosensitivity of laryngeal carcinoma through regulating autophagy

Dai

Zhou

et al. 2020

Head & Neck

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Background This study is to explore the role of curcumin and GLUT‐1 antisense oligodeoxynucleotides (AS‐ODN) on autophagy modulation‐initiated radiosensitivity. Methods BALB/c mice were employed to establish xenograft model using Tu212 cell. The expression of autophagy‐ and apoptosis‐related proteins was determined by WB. Autophagosome was observed under transmission electron microscope. Apoptosis of tumor tissue were detected by TUNEL staining. Results Combinations of curcumin and GLUT‐1 AS‐ODN with 10 Gy inhibited the tumor growth by inducing apoptosis of laryngeal cancer cells followed with the enhancement of autophagy. 3‐MA also had a promotion effect on irradiation‐mediated growth inhibition possibly by depressing PI3K and on curcumin/GLUT‐1 AS‐ODN‐mediated growth inhibition potentially by regulating autophagic events. Of note, a de‐escalation of radiotherapy dose (5 Gy) along with curcumin, GLUT‐1 AS‐ODN or 3‐MA produced a stronger effect than high dosage of radiotherapy (10 Gy) alone. Conclusions Curcumin and GLUT‐1 AS‐ODN improve the radiosensitivity of laryngeal carcinoma through regulating autophagy and inducing apoptosis.

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Targeted disruption of PI3K/Akt/mTOR signaling pathway, via PI3K inhibitors, promotes growth inhibitory effects in oral cancer cells

Cited by 48 publications

References 47 publications

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

ZnO Nanoparticles Induced Caspase-Dependent Apoptosis in Gingival Squamous Cell Carcinoma through Mitochondrial Dysfunction and p70S6K Signaling Pathway

Effect of combination of curcumin and GLUT‐1 AS‐ODN on radiosensitivity of laryngeal carcinoma through regulating autophagy

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