Effective co-delivery of nutlin-3a and p53 genes via core–shell microparticles for disruption of MDM2–p53 interaction and reactivation of p53 in hepatocellular carcinoma

Using core–shell microparticles encapsulating p53/β-CD-g-CS NPs and nutlin-3a effectively suppressed p53–MDM2 interaction and restored p53 apoptotic activity in cancer cells.

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Glycolysis Inhibition as a Strategy for Hepatocellular Carcinoma Treatment?

Current Cancer Drug Targets ◽

10.2174/1568009618666180430144441 ◽

2018 ◽

Vol 19 (1) ◽

pp. 26-40 ◽

Cited By ~ 9

Author(s):

A.P. Alves ◽

A.C. Mamede ◽

M.G. Alves ◽

P.F. Oliveira ◽

S.M. Rocha ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Cells ◽

Anticancer Agents ◽

Glucose Transporter ◽

Public Health Problem ◽

High Morbidity ◽

Curative Intent ◽

Malignant Liver Tumor ◽

Glucose Transporter 1 ◽

Inhibition Of Glycolysis

Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis. HCC, such as other cancer types, presents a clinically well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1). Such enzymes and proteins constitute potential targets for therapy. Indeed, for some of these targets, several inhibitors were already reported, such as 2-Deoxyglucose, Imatinib or Flavonoids. Although the inhibition of glycolysis presents a great potential for an anticancer therapy, the development of glycolytic inhibitors as a new class of anticancer agents needs to be more explored. Herein, we propose to summarize, discuss and present an overview on the different approaches to inhibit the glycolytic metabolism in cancer cells, which may be very effective in the treatment of HCC.

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Cytotoxicity, Oxidative Stress, Cell Cycle Arrest, and Mitochondrial Apoptosis after Combined Treatment of Hepatocarcinoma Cells with Maleic Anhydride Derivatives and Quercetin

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/2734976 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 16

Author(s):

Gabriela Carrasco-Torres ◽

Rafael Baltiérrez-Hoyos ◽

Erik Andrade-Jorge ◽

Saúl Villa-Treviño ◽

José Guadalupe Trujillo-Ferrara ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Maleic Anhydride ◽

Cancer Cells ◽

Combination Treatment ◽

Malignant Tumors ◽

Combined Treatment ◽

Current Data ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells

The inflammatory condition of malignant tumors continually exposes cancer cells to reactive oxygen species, an oxidizing condition that leads to the activation of the antioxidant defense system. A similar activation occurs with glutathione production. This oxidant condition enables tumor cells to maintain the energy required for growth, proliferation, and evasion of cell death. The objective of the present study was to determine the effect on hepatocellular carcinoma cells of a combination treatment with maleic anhydride derivatives (prooxidants) and quercetin (an antioxidant). The results show that the combination of a prooxidant/antioxidant had a cytotoxic effect on HuH7 and HepG2 liver cancer cells, but not on either of two normal human epithelial cell lines or on primary hepatocytes. The combination treatment triggered apoptosis in hepatocellular carcinoma cells by activating the intrinsic pathway and causing S phase arrest during cell cycle progression. There is also clear evidence of a modification in cytoskeletal actin and nucleus morphology at 24 and 48 h posttreatment. Thus, the current data suggest that the combination of two anticarcinogenic drugs, a prooxidant followed by an antioxidant, can be further explored for antitumor potential as a new treatment strategy.

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