Role of autophagy in resistance to oxaliplatin in hepatocellular carcinoma cells

Du, Hong; Yang, Weiping; Chen, Lin; Shi, Mingming; Seewoo, Varun; Wang, Jiayu; Lin, Andy; Liu, Zhuoran; Qiu, Weihua

doi:10.3892/or.2011.1464

Cited by 32 publications

(19 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acridine orange staining of live HepG2 and Hep3B cells showed increased AVO formation following SAMe pre-treatment (Figure 3A). Consistent with our previous results [4], I/H exposure increased AVOs amount in both HepG2 and Hep3B cells. Acute I/H with SAMe pre-treatment had no apparent influence on AVO formation in Hep3B cells, while a notable increase in AVOs was observed in HepG2 cells.…”

Section: Resultssupporting

confidence: 93%

See 1 more Smart Citation

GADD45β induction by S-adenosylmethionine inhibits hepatocellular carcinoma cell proliferation during acute ischemia-hypoxia

Shen

Seewoo

et al. 2016

Oncotarget

Self Cite

View full text Add to dashboard Cite

Growth arrest DNA damage-inducible gene 45β (GADD45β), which influences cell growth, apoptosis and cellular response to DNA damage, is downregulated in hepatocellular carcinoma (HCC). S-adenosylmethionine (SAMe) serves as an essential methyl donor in multiple metabolic pathways and is a polyamine and glutathione (GSH) precursor. In this study, we assessed the roles of GADD45β and SAMe in cell survival during acute ischemia-hypoxia (I/H). SAMe treatment induced growth of HL-7702 normal hepatic cells, but decreased the viability of HepG2 (p53 wild-type) and Hep3B (p53 null) HCC cells. Cells were exposed to I/H with or without SAMe pre-treatment. I/H exposure alone triggered HCC cell proliferation promoted by autophagy. SAMe pre-treatment restored GADD45β expression and activated HCC cell apoptosis and eliminated I/H-induced HCC cell proliferation. p53 loss blunted the response to SAMe and I/H exposure in Hep3B cells; thus, the inhibitory effect of SAMe on cell proliferation may be reduced in p53-null cells as compared to wild-type cells. These results indicate that GADD45β induction by SAMe inhibits HCC cell proliferation during I/H as a result of increased apoptosis, and that SAMe also protects normal hepatocytes from apoptotic cell death and promotes normal cell regeneration. SAMe should be considered a potential therapeutic agent for the management of HCC.

show abstract

Section: Resultssupporting

confidence: 93%

“…Despite recent progress in diagnostic and therapeutic management, hepatocellular carcinoma (HCC) patient prognosis remains poor [1–4]. The level of downregulation of growth arrest DNA damage-inducible gene 45β (GADD45b) in HCC is strongly correlated with increased tumor malignancy [5].…”

Section: Introductionmentioning

confidence: 99%

GADD45β induction by S-adenosylmethionine inhibits hepatocellular carcinoma cell proliferation during acute ischemia-hypoxia

Shen

Seewoo

et al. 2016

Oncotarget

Self Cite

View full text Add to dashboard Cite

show abstract

“…In oesophageal cancer cell, autophagy can promote these drug-resistant cancer cell survival and recovery following treatment with chemotherapeutics (18). In addition, autophagy may function importantly in HepG2 cell resistance to oxaliplatin and the resistance could be recovered apparently by inhibition of autophagy (19). Therefore, these results have indicated that autophagy may play an important role in the mechanism of the tumour cells resistant to anti-cancer drugs.…”

Section: Background and Evidencementioning

confidence: 91%

Autophagy Facilitates the Sorafenib Resistance of Hepatocellular Carcinoma Cells

Liu¹,

Cao²,

Jiang³

et al. 2014

West Indian Med J

View full text Add to dashboard Cite

Liver cancer is the second most frequent cause of cancer death in men and the sixth leading cause of cancer death in women. Hepatocellular carcinoma (HCC) represents the major subtype in liver cancer and its five-year survival rate remains very poor. Sorafenib, a molecular targeted therapeutic agent, was the first drug approved for the treatment of patients with HCC. However, the clinical response of sorafenib was seriously limited by drug resistance. Autophagy is an evolutionarily conserved mechanism among all eukaryotes. Recently, many studies have indicated that autophagy can be activated as a cellular protective mechanism in many tumour cells. Thus, we hypothesized that autophagy may play an important role in hepatocellular carcinoma's resistance to sorafenib. Although the exact role of autophagy in the sorafenib resistance of HCC is still complex and further studies are needed to be proven, at least it suggests that autophagy may be a new therapeutic target for the sorafenib resistance of HCC.

show abstract

“…These facts indicate that this enzyme could have an important role in resistance acquisition processes to different chemotherapeutic drugs. Furthermore, it has been shown that some of the PKM2 biological functions depend on the enzyme’s nuclear translocation which is promoted by different post-translational modifications such as tyrosine phosphorylation [ 15 – 17 ], lysine acetylation [ 18 ], or sumoylation [ 19 ] in response to the factors EGFR [ 20 ], IL-3 [ 21 ] or Oct-4 [ 22 ] respectively. While in the majority of the above mentioned cases PKM2 translocation results in the stimulation of cell proliferation, it has been demonstrated that after other kinds of stimuli like DNA damage or oxidative stress, PKM2 translocates to the nucleus of cells leading to the activation of cell death in a caspases and Bcl-2 independent manner [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

PKM2 Subcellular Localization Is Involved in Oxaliplatin Resistance Acquisition in HT29 Human Colorectal Cancer Cell Lines

et al. 2015

View full text Add to dashboard Cite

Chemoresistance is the main cause of treatment failure in advanced colorectal cancer (CRC). However, molecular mechanisms underlying this phenomenon remain to be elucidated. In a previous work we identified low levels of PKM2 as a putative oxaliplatin-resistance marker in HT29 CRC cell lines and also in patients. In order to assess how PKM2 influences oxaliplatin response in CRC cells, we silenced PKM2 using specific siRNAs in HT29, SW480 and HCT116 cells. MTT test demonstrated that PKM2 silencing induced resistance in HT29 and SW480 cells and sensitivity in HCT116 cells. Same experiments in isogenic HCT116 p53 null cells and double silencing of p53 and PKM2 in HT29 cells failed to show an influence of p53. By using trypan blue stain and FITC-Annexin V/PI tests we detected that PKM2 knockdown was associated with an increase in cell viability but not with a decrease in apoptosis activation in HT29 cells. Fluorescence microscopy revealed PKM2 nuclear translocation in response to oxaliplatin in HCT116 and HT29 cells but not in OXA-resistant HTOXAR3 cells. Finally, by using a qPCR Array we demonstrated that oxaliplatin and PKM2 silencing altered cell death gene expression patterns including those of BMF, which was significantly increased in HT29 cells in response to oxaliplatin, in a dose and time-dependent manner, but not in siPKM2-HT29 and HTOXAR3 cells. BMF gene silencing in HT29 cells lead to a decrease in oxaliplatin-induced cell death. In conclusion, our data report new non-glycolytic roles of PKM2 in response to genotoxic damage and proposes BMF as a possible target gene of PKM2 to be involved in oxaliplatin response and resistance in CRC cells.

show abstract

Role of autophagy in resistance to oxaliplatin in hepatocellular carcinoma cells

Cited by 32 publications

References 26 publications

GADD45β induction by S-adenosylmethionine inhibits hepatocellular carcinoma cell proliferation during acute ischemia-hypoxia

GADD45β induction by S-adenosylmethionine inhibits hepatocellular carcinoma cell proliferation during acute ischemia-hypoxia

Autophagy Facilitates the Sorafenib Resistance of Hepatocellular Carcinoma Cells

PKM2 Subcellular Localization Is Involved in Oxaliplatin Resistance Acquisition in HT29 Human Colorectal Cancer Cell Lines

Contact Info

Product

Resources

About