Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer

Khan, Khushbukhat; Quispe, Cristina; Javed, Zeeshan; Iqbal, Muhammad Javed; Sadia, Haleema; Raza, Shahid; Irshad, Asma; Salehi, Bahare; Reiner, Željko; Sharifi‐Rad, Javad

doi:10.1186/s12935-020-01660-7

Cited by 47 publications

(35 citation statements)

References 145 publications

(142 reference statements)

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“…Inhibiting the different processes of the PI3K/AKT/m-TOR pathway is a common strategy for the treatment of human malignant tumors [ 58 ]. Many bioactive flavonoids, such as collagen and paclitaxel, have been reported to down-regulate the expressions of proteins such as p-PI3K, p-AKT, and p-mTOR by inhibiting PI3K/AKT/mTOR pathway in HCC [ 59 , 60 ]. Our study shows that the protein levels of PI3K, p-PI3K, p-AKT, and p-mTOR were down-regulated following 4-HD treatment, while the expressions of AKT and mTOR proteins were up-regulated, indicating that the suppression effect of 4-HD on the PI3K/AKT/mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

4-Hydroxyderricin Promotes Apoptosis and Cell Cycle Arrest through Regulating PI3K/AKT/mTOR Pathway in Hepatocellular Cells

Gao

Jiang

et al. 2021

Foods

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4-hydroxyderricin (4-HD), as a natural flavonoid compound derived from Angelica keiskei, has largely unknown inhibition and mechanisms on liver cancer. Herein, we investigated the inhibitory effects of 4-HD on hepatocellular carcinoma (HCC) cells and clarified the potential mechanisms by exploring apoptosis and cell cycle arrest mediated via the PI3K/AKT/mTOR signaling pathway. Our results show that 4-HD treatment dramatically decreased the survival rate and activities of HepG2 and Huh7 cells. The protein expressions of apoptosis-related genes significantly increased, while those related to the cell cycle were decreased by 4-HD. 4-HD also down-regulated PI3K, p-PI3K, p-AKT, and p-mTOR protein expression. Moreover, PI3K inhibitor (LY294002) enhanced the promoting effect of 4-HD on apoptosis and cell cycle arrest in HCC cells. Consequently, we demonstrate that 4-HD can suppress the proliferation of HCC cells by promoting the PI3K/AKT/mTOR signaling pathway mediated apoptosis and cell cycle arrest.

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Section: Discussionmentioning

confidence: 99%

4-Hydroxyderricin Promotes Apoptosis and Cell Cycle Arrest through Regulating PI3K/AKT/mTOR Pathway in Hepatocellular Cells

Gao

Jiang

et al. 2021

Foods

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“…PI3K/AKT signaling pathway is an important intracellular functional regulatory pathway that involves in a variety of biological process including proliferation, apoptosis, migration, invasion, and oxidative stress [ 49 , 50 ]. These biological functions enable it to participate in the regulation of a variety of diseases, such as cancer [ 10 ], diabetes [ 51 ], neurodegenerative diseases [ 52 ], and gastrointestinal disorders [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Quercetin Improves Mitochondrial Function and Inflammation in H2O2-Induced Oxidative Stress Damage in the Gastric Mucosal Epithelial Cell by Regulating the PI3K/AKT Signaling Pathway

Yao

Mei

Mao

2021

Evidence-Based Complementary and Alternative Medicine

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Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, the therapeutic strategy of which it is limited due to its complex pathogenesis. Oxidative stress-induced damage in gastric mucosal epithelial cells is related to the pathogenesis and development of FD. Quercetin (Que) is one of the active ingredients of Zhishi that showed antioxidant, antiapoptotic, and anti-inflammatory effects. The aim of this study is to investigate the effect of Que on oxidative stress-induced gastric mucosal epithelial cells damage and its underlying molecular mechanism. The gastric mucosal epithelial cell line GES-1 was treated with 200 μM of H2O2 to construct an oxidative stress-induced damage model. The H2O2 cells were then administrated with different concentrations of Que. The results indicated that high concentration of Que (100 μM) showed cytotoxicity in H2O2-induced GES-1 cells. However, appropriate concentration of Que (25 and 50 μM) alleviated the oxidative stress damage induced by H2O2, as demonstrated by the increase of proliferation, decrease of ROS generation, apoptosis, inflammation, and alleviation of mitochondrial function and cell barrier. In addition, Que increased the activation of phosphorylation of PI3K and AKT decreased by H2O2. To investigate whether Que alleviated the oxidative stress damage in GES-1 cells by the PI3K/AKT signaling pathway, the GES-1 cells were treated with Que (25 μM) combined with and without LY294002, the PI3K inhibitor. The results showed that LY294002 suppressed the alleviation effect on Que in H2O2-induced GES-1 cells. In conclusion, the current study demonstrates that Que alleviates oxidative stress damage in GES-1 cells by improving mitochondrial function and mucosal barrier and suppressing inflammation through regulating the PI3K/AKT signaling pathway, indicating the potential therapeutic effects of Que on FD.

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“…In BCa, no study has investigated the inhibition of PI3 Kγ in TAMs. It seems that the PI3 K signaling pathway is essential in bladder tumor cells, regulating their proliferation, migration, invasiveness and metastasis [212]. For that, several PI3 K inhibitors have been tested in clinical trials (Table 3).…”

Section: Phosphoinositide 3-kinase (Pi3 K) Inhibitorsmentioning

confidence: 99%

Tumor-Associated Macrophages in Bladder Cancer: Biological Role, Impact on Therapeutic Response and Perspectives for Immunotherapy

Leblond

Zdimerova

Desponds

et al. 2021

Cancers

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Tumor-associated macrophages (TAMs) are one of the most abundant infiltrating immune cells of solid tumors. Despite their possible dual role, i.e., pro- or anti-tumoral, there is considerable evidence showing that the accumulation of TAMs promotes tumor progression rather than slowing it. Several strategies are being developed and clinically tested to target these cells. Bladder cancer (BCa) is one of the most common cancers, and despite heavy treatments, including immune checkpoint inhibitors (ICIs), the overall patient survival for advanced BCa is still poor. TAMs are present in bladder tumors and play a significant role in BCa development. However, few investigations have analyzed the effect of targeting TAMs in BCa. In this review, we focus on the importance of TAMs in a cancerous bladder, their association with patient outcome and treatment efficiency as well as on how current BCa treatments impact these cells. We also report different strategies used in other cancer types to develop new immunotherapeutic strategies with the aim of improving BCa management through TAMs targeting.

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Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer

Cited by 47 publications

References 145 publications

4-Hydroxyderricin Promotes Apoptosis and Cell Cycle Arrest through Regulating PI3K/AKT/mTOR Pathway in Hepatocellular Cells

4-Hydroxyderricin Promotes Apoptosis and Cell Cycle Arrest through Regulating PI3K/AKT/mTOR Pathway in Hepatocellular Cells

Quercetin Improves Mitochondrial Function and Inflammation in H2O2-Induced Oxidative Stress Damage in the Gastric Mucosal Epithelial Cell by Regulating the PI3K/AKT Signaling Pathway

Tumor-Associated Macrophages in Bladder Cancer: Biological Role, Impact on Therapeutic Response and Perspectives for Immunotherapy

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