Association between reversal of multidrug resistance by methyl jasmonate and P-glycoprotein ATPase activity in hepatocellular carcinoma

Wang, Changfa; Wang, Yaqin; Huang, Feizhou; Nie, Wei; Liu, Xun-yang; Jiang, Xianzhen

doi:10.1177/0300060513483401

Cited by 3 publications

(1 citation statement)

References 34 publications

(32 reference statements)

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“…The Warburg effect showed that tumor cells prefer glycolysis to oxidative phosphorylation (OXPHOS) in terms of glucose metabolism even in the presence of sufficient amounts of oxygen. This is because glycolysis results in the production of fatty acids, nucleic acids, proteins and membrane phospholipids that combine with ATP to meet the demand for tumor proliferation [ 5 – 7 ]. Hexokinase (HK) is not only the first enzyme in the glycolytic pathway but is the rate-limiting enzyme [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Methyl jasmonate leads to necrosis and apoptosis in hepatocellular carcinoma cells via inhibition of glycolysis and represses tumor growth in mice

Chen

Wang

et al. 2017

Oncotarget

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Methyl jasmonate has recently been found to have anti-cancer activity. Methyl jasmonate detached hexokinase 2 from a voltage dependent anion channel causing a reduction in mitochondrial transmembrane potential that led to the release of cytochrome C and apoptosis inducing factor resulting in intrinsic apoptosis. Blocked adenosine triphosphate synthesis caused by mitochondrial injury hampered oxidative phosphorylation and led to cell necrosis. The results were applied to the in vivo treatment of nude mice with a satisfactory effect. Collectively, our results suggest that methyl jasmonate may be an adjuvant therapy for liver tumors due to its mechanism in cancer cells compared to that in normal cells: The major function is to inhibit glycolysis instead of changing aerobic metabolism.

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Section: Introductionmentioning

confidence: 99%

Methyl jasmonate leads to necrosis and apoptosis in hepatocellular carcinoma cells via inhibition of glycolysis and represses tumor growth in mice

Chen

Wang

et al. 2017

Oncotarget

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E-cadherin increasing multidrug resistance protein 1 via hypoxia-inducible factor-1α contributes to multicellular resistance in colorectal cancer

Liu

Wang

et al. 2015

Tumor Biol.

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When cancer cells have been cultured as three-dimensional (3D) cultures or in vivo, they decrease sensitivity to anticancer drugs. This is called multicellular resistance, and the mechanism is not fully understood. Here, we report that E-cadherin increasing multidrug resistance protein 1 (MDR1) via hypoxia-inducible factor-1α (HIF-1α) contributes to multicellular resistance in colorectal cancer. The MDR1 protein level was higher in 3D cultures than in monolayer cells. When dispersed cells from 3D cultures were grown as monolayer cells again, the MDR1 protein level decreased to the similar level of cells maintained as monolayer all through. Knockdown of MDR1 significantly decreased multicellular resistance. Knockdown of E-cadherin decreased MDR1 in 3D cultures but did not detectably change MDR1 in monolayer cells. E-cadherin was expressed uniformly in 3D cultures while the MDR1 protein level was higher in the center of 3D cultures than in the peripheral part. Knockdown of E-cadherin decreased E-cadherin uniformly in 3D cultures but mainly decreased MDR1 at the center of 3D cultures. These suggest that knockdown of E-cadherin decreasing MDR1 may be by an indirect mechanism. HIF-1α was remarkably increased in 3D cultures. Knockdown of E-cadherin decreased intercellular junctions, increased intercellular space, and decreased HIF-1α in 3D cultures. Knockdown of HIF-1α decreased MDR1 in 3D cultures. Knockdown of E-cadherin increased β-catenin uniformly in 3D cultures, and knockdown of β-catenin decreased MDR1 what was opposite to knockdown of E-cadherin decreasing MDR1. Our data reveal that knockdown of E-cadherin decreasing MDR1 via HIF-1α is involved in the mechanism of multicellular resistance in colorectal cancer. Though β-catenin is also involved in the mechanism, it does not play a dominant role.

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Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication

Lee¹

2015

WJBC

123

115

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Aerobic glycolysis, i.e. , the Warburg effect, may contribute to the aggressive phenotype of hepatocellular carcinoma. However, increasing evidence highlights the limitations of the Warburg effect, such as high mitochondrial respiration and low glycolysis rates in cancer cells. To explain such contradictory phenomena with regard to the Warburg effect, a metabolic interplay between glycolytic and oxidative cells was proposed, i.e. , the "reverse Warburg effect". Aerobic glycolysis may also occur in the stromal compartment that surrounds the tumor; thus, the stromal cells feed the cancer cells with lactate and this interaction prevents the creation of an acidic condition in the tumor microenvironment. This concept provides great heterogeneity in tumors, which makes the disease difficult to cure using a single agent. Understanding metabolic flexibility by lactate shuttles offers new perspectives to develop treatments that target the hypoxic tumor microenvironment and overcome the limitations of glycolytic inhibitors.

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Association between reversal of multidrug resistance by methyl jasmonate and P-glycoprotein ATPase activity in hepatocellular carcinoma

Abstract: The combined use of methyl jasmonate and the FAP regimen might be a novel strategy for overcoming the multidrug resistance often observed in hepatocellular carcinoma.

Cited by 3 publications

References 34 publications

Methyl jasmonate leads to necrosis and apoptosis in hepatocellular carcinoma cells via inhibition of glycolysis and represses tumor growth in mice

Methyl jasmonate leads to necrosis and apoptosis in hepatocellular carcinoma cells via inhibition of glycolysis and represses tumor growth in mice

E-cadherin increasing multidrug resistance protein 1 via hypoxia-inducible factor-1α contributes to multicellular resistance in colorectal cancer

Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication

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