Deoxyshikonin Inhibits Viability and Glycolysis by Suppressing the Akt/mTOR Pathway in Acute Myeloid Leukemia Cells

Wu, Huijuan; Zhao, Haixia; Chen, Li

doi:10.3389/fonc.2020.01253

Cited by 25 publications

(16 citation statements)

References 34 publications

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“…The half maximal inhibitory concentrations (IC50) of DSK were 8.995 µM in HSC-3 cells and 8.274 µM in SCC-9 cells. This finding, in accordance with the tumor suppressive features observed in other tumor types [8][9][10], points out a therapeutic potential of DSK in OSCC.…”

Section: Dsk Dose-dependently Decreases Tongue Cancer Cell Viabilitysupporting

confidence: 88%

Deoxyshikonin Mediates Heme Oxygenase-1 Induction and Apoptotic Response via p38 Signaling in Tongue Cancer Cell Lines

Chuang

Lin

et al. 2022

IJMS

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Deoxyshikonin (DSK), a phytochemical constituent, has been documented to elicit various oncostatic properties alone or in combination with established therapeutics. However, its role in restraining oral squamous cell carcinoma (OSCC) is mostly unclear. Here, we examined the tumor-suppressive effect of DSK and explored the molecular mechanisms underlying DSK’s activities on controlling oral cancer. Our results showed that DSK dose-dependently lessened the cell viability of tongue cancer cell lines, involving induction of cell cycle arrest at the sub-G1 phase and apoptotic cell death. Moreover, a unique signature of apoptosis-related proteins, including augmented nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) expression and caspase activation, was observed in DSK-treated tongue cancer cell lines. Furthermore, DSK-mediated upregulation of HO-1 and cleavage of caspase-9 and -3 were significantly inhibited by pharmacological blockage of p38 kinase. Collectively, these data revealed that DSK halted cell cycle progression and elicited cell apoptosis in tongue cancer cell lines, reshaping a p38-dependent profile of apoptotic proteome. Our findings provided novel insights into the therapeutic implications of a natural compound on the management of OSCC.

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Section: Dsk Dose-dependently Decreases Tongue Cancer Cell Viabilitysupporting

confidence: 88%

Deoxyshikonin Mediates Heme Oxygenase-1 Induction and Apoptotic Response via p38 Signaling in Tongue Cancer Cell Lines

Chuang

Lin

et al. 2022

IJMS

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“…mTOR is an important regulator of cell metabolism. Studies have demonstrated that mTOR-mediated glycolysis plays an important role in the tumor cell proliferation and migration 30 , 31 . Therefore, we suspect that mTOR may be the hinge that links CD36 to glycolysis.…”

Section: Resultsmentioning

confidence: 99%

The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis

et al. 2021

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Metabolic reprogramming is a new hallmark of cancer but it remains poorly defined in hepatocellular carcinogenesis (HCC). The fatty acid receptor CD36 is associated with both lipid and glucose metabolism in the liver. However, the role of CD36 in metabolic reprogramming in the progression of HCC still remains to be elucidated. In the present study, we found that CD36 is highly expressed in human HCC as compared with non-tumor hepatic tissue. CD36 overexpression promoted the proliferation, migration, invasion, and in vivo tumor growth of HCC cells, whereas silencing CD36 had the opposite effects. By analysis of cell metabolic phenotype, CD36 expression showed a positive association with extracellular acidification rate, a measure of glycolysis, instead of oxygen consumption rate. Further experiments verified that overexpression of CD36 resulted in increased glycolysis flux and lactic acid production. Mechanistically, CD36 induced mTOR-mediated oncogenic glycolysis via activation of Src/PI3K/AKT signaling axis. Pretreatment of HCC cells with PI3K/AKT/mTOR inhibitors largely blocked the tumor-promoting effect of CD36. Our findings suggest that CD36 exerts a stimulatory effect on HCC growth and metastasis, through mediating aerobic glycolysis by the Src/PI3K/AKT/mTOR signaling pathway.

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“…By inhibiting glycolysis and its key enzymes, the growth of tumor cells can be inhibited, the apoptosis of tumor cells can be accelerated, and the resistance of tumor cells to treatment can be reversed, so as to achieve effective anti-tumor activity. 19 Previous studies have confirmed that PKM2 is a key enzyme regulating glucose metabolism in solid tumors such as breast cancer. 20,21 Our study found that PKM2 was also highly expressed in AL, which may be closely related to the vigorous glycolytic metabolic activity characterizing leukemia cells.…”

Section: Discussionmentioning

confidence: 92%

High Expression of PKM2 Was Associated with the Poor Prognosis of Acute Leukemia

Huang

Chen

Xie

et al. 2021

CMAR

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Purpose: To explore the clinical significance of plasma pyruvate kinase M2 (PKM2) in assessing the incidence and prognosis of acute leukemia. Methods: Plasma samples from 56 acute myeloid leukemia (AML) patients, 40 acute lymphoblastic leukemia (ALL) patients, and 66 plasma samples from healthy individuals were collected. The level of plasma PKM2 was detected by enzyme-linked immunosorbent assay. The clinical significance of PKM2 in acute leukemia was assessed by analyzing receiver operating characteristic and survival curves. Results:The plasma levels of PKM2 in AML or ALL patients were significantly higher than those in healthy individuals, respectively. PKM2 can be used as a potential diagnostic index with the AUC of 0.827 for AML and 0.837 for ALL. The level of plasma PKM2 in ALL patients with a BCR/ABL-positive genotype was significantly higher than that in patients with a BCR/ABL-negative genotype (p<0.05). The event-free survival and the overall survival of acute leukemia patients with higher PKM2 expression was worse than those with lower PKM2 expression. Conclusion: This study showed that higher levels of PKM2 was negatively correlated with the prognosis of acute leukemia. Therefore, PKM2 can be used as a potential index to assess the incidence and prognosis of acute leukemia.

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Deoxyshikonin Inhibits Viability and Glycolysis by Suppressing the Akt/mTOR Pathway in Acute Myeloid Leukemia Cells

Cited by 25 publications

References 34 publications

Deoxyshikonin Mediates Heme Oxygenase-1 Induction and Apoptotic Response via p38 Signaling in Tongue Cancer Cell Lines

Deoxyshikonin Mediates Heme Oxygenase-1 Induction and Apoptotic Response via p38 Signaling in Tongue Cancer Cell Lines

The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis

High Expression of PKM2 Was Associated with the Poor Prognosis of Acute Leukemia

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