Autophagy and glycolysis independently attenuate silibinin-induced apoptosis in human hepatocarcinoma HepG2 and Hep3B cells

Yang, Jing; Sun, Yu; Xu, Fanxing; Liu, W; Hayashi, Toshihiko; Mizuno, Kazunori; Hattori, Shunji; Fujisaki, Hitomi; Ikejima, Takashi

doi:10.1177/09603271211017609

Cited by 8 publications

(4 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another limitation of the studies is that some of them did not investigate the interaction between autophagy and apoptosis in HCC. According to studies, autophagy and apoptosis show interactions in normal and cancerous cells and even in different diseases, and autophagy can sometimes inhibit apoptosis [97][98][99]. However, this role has been ignored in some studies on HCC.…”

Section: Autophagy and Apoptosis Interactionmentioning

confidence: 99%

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

et al. 2023

View full text Add to dashboard Cite

Autophagy is an evolutionarily conserved process that plays a role in regulating homeostasis under physiological conditions. However, dysregulation of autophagy is observed in the development of human diseases, especially cancer. Autophagy has reciprocal functions in cancer and may be responsible for either survival or death. Hepatocellular carcinoma (HCC) is one of the most lethal and common malignancies of the liver, and smoking, infection, and alcohol consumption can lead to its development. Genetic mutations and alterations in molecular processes can exacerbate the progression of HCC. The function of autophagy in HCC is controversial and may be both tumor suppressive and tumor promoting. Activation of autophagy may affect apoptosis in HCC and is a regulator of proliferation and glucose metabolism. Induction of autophagy may promote tumor metastasis via induction of EMT. In addition, autophagy is a regulator of stem cell formation in HCC, and pro-survival autophagy leads to cancer cell resistance to chemotherapy and radiotherapy. Targeting autophagy impairs growth and metastasis in HCC and improves tumor cell response to therapy. Of note, a large number of signaling pathways such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs regulate autophagy in HCC. Moreover, regulation of autophagy (induction or inhibition) by antitumor agents could be suggested for effective treatment of HCC. In this paper, we comprehensively review the role and mechanisms of autophagy in HCC and discuss the potential benefit of targeting this process in the treatment of the cancer. Graphical abstract

show abstract

Section: Autophagy and Apoptosis Interactionmentioning

confidence: 99%

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Similarly, the long non-coding RNAs (lncRNAs)-hsa-miR-4443-AKT1 pathway responds positively to baicalein treatment[ 35 ]. Studies have further revealed that silibinin induces autophagy through the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway and induces apoptosis by up-regulated p21/cyclin-dependent kinases (CDK) 4 and p27/CDK4 complexes, and down-regulated Rb-phosphorylation and E2F1/DP1 complex[ 36 , 37 ]. Lee and Kwon[ 38 ] demonstrated that luteolin causes ER stress in p53-wild type HepG2 cells and Hep3B cells[ 38 ].…”

Section: Augmented Local Controlmentioning

confidence: 99%

Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma

Lai¹,

Lin²,

Jeng³

et al. 2023

World J Gastrointest Oncol

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the fourth leading cause of cancer-related deaths in the world. HCC has a reported recurrence rate of 70%-80% after 5 years of follow-up. Controlling tumor recurrence is the most critical factor associated with HCC mortality. Conventional salvage therapies for recurrent HCC include re-hepatectomy or liver transplantation, transcatheter arterial chemoembolization, Y-90, target therapy, and immunotherapy; however, these conventional treatment modalities have yet to achieve consistently favorable outcomes. Meanwhile, previous studies have demonstrated that conventional therapies in combination with traditional Chinese medicine (TCM), acupuncture, moxibustion or dietary supplements could notably benefit patients with HCC recurrence by strengthening and augmenting the overall management strategy. However, systemic reviews related to the interactions between complementary therapies and conventional therapy in recurrent HCC are limited. In this review, we discuss the molecular mechanisms underlying the functions of complementary therapies for recurrent HCC, which include augmenting the local control to improve the congestion status of primary tumors and reducing multicentric tumor occurrence via inducing autophagy, apoptosis or cell cycle arrest. TCM and its derivatives may play important roles in helping to control HCC recurrence by inhibiting epithelial-mesenchymal transition, migration, invasion, and metastasis, inhibiting cancer stem cells, and ameliorating drug resistance.

show abstract

“…It was revealed that increased aerobic glycolysis in nasopharyngeal carcinoma cells via the IRF2/CENP-N/AKT axis promoted malignant biological behavior while inhibiting apoptosis ( Qi et al, 2021 ). In hepatocellular carcinoma (HCC), aerobic glycolysis was also found to inhibit Silibinin-triggered apoptosis in human HCC HepG2 and Hep3B cells ( Yang et al, 2021 ). In addition to the glycolysis-mediated suppression of tumor cell apoptosis, its metabolite lactate accumulates in the TME, leading to acidification of the extracellular pH and immunosuppression, which, in turn, affect the TME ( de la Cruz-López et al, 2019 ).…”

Section: The Significance and Related Mechanism Of Glycolysis In Tumo...mentioning

confidence: 99%

The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment

Zhou

Duan

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

It is well known that tumor cells rely mainly on aerobic glycolysis for energy production even in the presence of oxygen, and glycolysis is a known modulator of tumorigenesis and tumor development. The tumor microenvironment (TME) is composed of tumor cells, various immune cells, cytokines, and extracellular matrix, among other factors, and is a complex niche supporting the survival and development of tumor cells and through which they interact and co-evolve with other tumor cells. In recent years, there has been a renewed interest in glycolysis and the TME. Many studies have found that glycolysis promotes tumor growth, metastasis, and chemoresistance, as well as inhibiting the apoptosis of tumor cells. In addition, lactic acid, a metabolite of glycolysis, can also accumulate in the TME, leading to reduced extracellular pH and immunosuppression, and affecting the TME. This review discusses the significance of glycolysis in tumor development, its association with the TME, and potential glycolysis-targeted therapies, to provide new ideas for the clinical treatment of tumors.

show abstract

Autophagy and glycolysis independently attenuate silibinin-induced apoptosis in human hepatocarcinoma HepG2 and Hep3B cells

Cited by 8 publications

References 56 publications

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma

The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment

Contact Info

Product

Resources

About