An Anti-tumorigenic Role of the Warburg Effect at Emergence of Transformed Cells

Ishibashi, Kojiro; Egami, Riku; Nakai, Kazuki; Kon, Shunsuke

doi:10.1247/csf.18018

Cited by 6 publications

(4 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Warburg effect allows tumor cells to undergo aerobic glycolysis to provide energy, even in the presence of sufficient oxygen, leading to increased glucose uptake and lactate production (30,31). This characteristic of glucose metabolism renders tumor cells more adaptable to hypoxia and contributes to cancer progression (32,33). Therefore, inhibiting aerobic glycolysis and then blocking the energy metabolism of neoplastic cells may constitute an effective antitumor treatment.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA inhibits cell growth by suppressing SIX1‑induced aerobic glycolysis in non‑small cell lung cancer cells

Chen²,

Qin³

et al. 2022

Oncol Lett

View full text Add to dashboard Cite

Aerobic glycolysis plays a key role in cancer cell metabolism and contributes to tumorigenesis, including that of non-small cell lung cancer (NSCLC). Tanshinone IIA (Tan IIA), an active compound of Salvia miltiorrhiza, exhibits antitumor properties. Multiple mechanisms are involved in the antitumor action of Tan IIA in lung cancer, such as inhibiting cell growth, promoting cell apoptosis and influencing cellular metabolism. However, the effects of Tan IIA on NSCLC cells and its mechanisms of action remain unclear. The present study shows Tan IIA dose-dependently attenuated the growth of NSCLC cells and in vitro in a dose-dependent manner. Moreover, Tan IIA markedly decreased the ATP level, glucose uptake and lactate production in the NSCLC cells in vitro. Tan IIA also inhibited tumor growth in a xenograft model in vivo. Mechanically, Tan IIA treatment decreased sine oculis homeobox homolog 1 (SIX1) mRNA and protein levels, thus leading to the downregulation of pyruvate kinase isozyme M2, hexokinase 2 and lactate dehydrogenase A (LDHA) expression in A549 cells. SIX1 knockdown with small interfering-RNA inhibited glycolysis in NSCLC cells, suggesting that SIX1 plays a role in the antitumor effect of Tan IIA on NSCLC cells. More importantly, it was demonstrated that SIX1 expression was stimulated in patients with NSCLC and was positively correlated with the LDH serum level. Finally, SIX1 low expression levels predicted the poor prognosis of patients with NSCLC. In conclusion, the present study showed that Tan IIA functioned as an anti-glycolysis agent in NSCLC cells by downregulating SIX1 expression and inhibiting cell proliferation.

show abstract

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA inhibits cell growth by suppressing SIX1‑induced aerobic glycolysis in non‑small cell lung cancer cells

Chen²,

Qin³

et al. 2022

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…10,11 Extrusion of altered, potentially preneoplastic cells can also be accomplished directly by normal surrounding counterparts through a process that has been referred to as epithelial defense against cancer (EDAC). 12,13 For example, altered cytoskeletal interactions between normal cells and Ras G12V -transformed cells were able to trigger removal of the latter from mouse intestinal epithelium. 11 Moreover, the efficiency of this protective strategy is susceptible to modulation by environmental influences.…”

Section: Aging and The Emergence Of Rare Mutated Cellsmentioning

confidence: 99%

Dietary patterns and the neoplastic‐prone tissue landscape of old age

Marongiu

Laconi

2020

Aging and Cancer

View full text Add to dashboard Cite

There is now sufficient evidence to indicate that aging is associated with the emergence of a clonogenic and neoplastic-prone tissue landscape, which fuels early stages of cancer development and helps explaining the rise in cancer incidence and mortality in older individuals. Dietary interventions are among the most effective approaches to delay aging and age-related diseases, including cancer. Reduced caloric intake has been, historically, the most intensely investigated strategy. Recent findings point to a critical role of a long fasting interval in mediating some of the beneficial effects of caloric restriction. Time-restricted feeding, intermittent fasting, and fasting mimicking diets are being proposed for their potential to prolong healthy life span and to delay late-onset diseases such as neoplasia. Evidence will be discussed suggesting that the effects of these dietary regimens are mediated, at least in part, through retardation of age-related functional changes at cell and tissue level, including a delay in the emergence of the neoplastic-prone tissue microenvironment.

show abstract

“…Enhanced glucose consumption and lactate excretion promote the Warburg effect, which is associated with oncogenic growth [ 9 ]. The Warburg effect is one of the hallmarks of cancer cells and is characterized by enhanced aerobic glycolysis, and the Warburg effect provides a theory of an inhibitory role in tumorigenesis [ 10 ]. Galangin reverses the Warburg effect in hepatocellular carcinoma cells, inhibits hepatocellular carcinoma cell proliferation, and is associated with glycolytic pathways [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Apigenin Suppresses the Warburg Effect and Stem-like Properties in SOSP-9607 Cells by Inactivating the PI3K/Akt/mTOR Signaling Pathway

Shi

Lian

Jia

2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Osteosarcoma (OS) is a prevalent primary malignant bone tumor that commonly occurs in children and adolescents. Apigenin (4′,5,7-trihydroxyflavone) is one of the most researched phenolic compounds that exhibits antitumor effects in several cancers. The aim of the current study was to investigate the effect and underlying mechanisms of apigenin on OS. To address this, OS cells (SOSP-9607) were treated with different concentrations of apigenin. The proliferation, migration, invasion, stem-like properties, and Warburg effect of apigenin-treated OS cells were evaluated. Apigenin was found to suppress the proliferation of SOSP-9607 cells and inhibit epithelial-mesenchymal transition, as indicated by decreased number of migrated and invaded cells, decreased protein expression of vimentin, and increased protein expression of E-cadherin. Additionally, apigenin suppressed tumorsphere formation and reduced the proportion of SOSP-9607 cells with positive expression of the stem cell-related markers Nanog and OCT-4. Apigenin inhibited the Warburg effect in SOSP-9607 cells, as demonstrated by decreased glucose and lactic acid levels, increased citrate and ATP levels, and downregulation of GLUT1, HK1, and LDHA, which are metabolism-related enzymes related to the Warburg effect. Moreover, apigenin inhibited the phosphorylation of PI3K, Akt, and mTOR in SOSP-9607 cells. Collectively, these results indicate that apigenin suppresses the Warburg effect and stem-like properties in SOSP-9607 cells, which may be mediated by PI3K/Akt/mTOR signaling, thus, providing a novel strategy for OS treatment.

show abstract

An Anti-tumorigenic Role of the Warburg Effect at Emergence of Transformed Cells

Cited by 6 publications

References 56 publications

Tanshinone IIA inhibits cell growth by suppressing SIX1‑induced aerobic glycolysis in non‑small cell lung cancer cells

Tanshinone IIA inhibits cell growth by suppressing SIX1‑induced aerobic glycolysis in non‑small cell lung cancer cells

Dietary patterns and the neoplastic‐prone tissue landscape of old age

Apigenin Suppresses the Warburg Effect and Stem-like Properties in SOSP-9607 Cells by Inactivating the PI3K/Akt/mTOR Signaling Pathway

Contact Info

Product

Resources

About