The role of ROS-induced autophagy in hepatocellular carcinoma

Yuan, Xingxing; Wang, Bingyu; Yang, Lei; Zhang, Yali

doi:10.1016/j.clinre.2018.01.005

Cited by 46 publications

(30 citation statements)

References 64 publications

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“…Reactive oxygen species (ROS) in non-pathological concentrations act as second messengers involved in several signal transduction pathways that regulate processes such as cell growth, proliferation and differentiation [ 20 ]. Therefore, cells have detoxification mechanisms that maintain a redox balance since, if they are altered, excessive production of ROS can lead to a situation of oxidative stress, which plays an important role in apoptosis and in the beginning of neoplasia development.…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative and Pro-Apoptotic Effect of Uvaol in Human Hepatocarcinoma HepG2 Cells by Affecting G0/G1 Cell Cycle Arrest, ROS Production and AKT/PI3K Signaling Pathway

et al. 2020

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Natural products have a significant role in the development of new drugs, being relevant the pentacyclic triterpenes extracted from Olea europaea L. Anticancer effect of uvaol, a natural triterpene, has been scarcely studied. The aim of this study was to understand the anticancer mechanism of uvaol in the HepG2 cell line. Cytotoxicity results showed a selectivity effect of uvaol with higher influence in HepG2 than WRL68 cells used as control. Our results show that uvaol has a clear and selective anticancer activity in HepG2 cells supported by a significant anti-migratory capacity and a significant increase in the expression of HSP-60. Furthermore, the administration of this triterpene induces cell arrest in the G0/G1 phase, as well as an increase in the rate of cell apoptosis. These results are supported by a decrease in the expression of the anti-apoptotic protein Bcl2, an increase in the expression of the pro-apoptotic protein Bax, together with a down-regulation of the AKT/PI3K signaling pathway. A reduction in reactive oxygen species (ROS) levels in HepG2 cells was also observed. Altogether, results showed anti-proliferative and pro-apoptotic effect of uvaol on hepatocellular carcinoma, constituting an interesting challenge in the development of new treatments against this type of cancer.

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Section: Introductionmentioning

confidence: 99%

Antiproliferative and Pro-Apoptotic Effect of Uvaol in Human Hepatocarcinoma HepG2 Cells by Affecting G0/G1 Cell Cycle Arrest, ROS Production and AKT/PI3K Signaling Pathway

et al. 2020

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“…In physiological conditions, the production and removal of ROS in liver are in dynamic balance. When the balance is destroyed, oxidative stress will be enhanced to injure hepatocytes . It is well known that mitochondrial dysfunction is related to the increase in ROS .…”

Section: Introductionmentioning

confidence: 99%

Sirtuin3 deficiency exacerbates carbon tetrachloride−induced hepatic injury in mice

Shen

et al. 2018

J Biochem & Molecular Tox

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Sirtuin3 (SIRT3) plays an important role in maintaining normal mitochondrial function and alleviating oxidative stress. After carbon tetrachloride (CCl 4 ) administration, the expression of SIRT3 decreased in the liver of mice, which indicated that the SIRT3 might play a crucial role during chemical-induced acute hepatic injury. To verify the hypothesis, CCl 4 was given to induce acute hepatic injury in SIRT3 knockout (KO) mice and wild-type (WT) mice. CCl 4 -induced liver injury was more severe in SIRT3 KO mice compared with the WT mice. In addition, the oxidative stress induced by CCl 4 was enhanced in the SIRT3 KO mice. Furthermore, the increased expression of dynamin-related protein 1 was also aggravated in SIRT3 KO mice after CCl 4 administration. In conclusion, our study demonstrated that SIRT3 deficiency exacerbated CCl 4 -induced impairment of the liver in mice, and the mechanism might be related to enhanced oxidative stress. K E Y W O R D Scarbon tetrachloride (CCl 4 ), liver, oxidative stress, sirtuin3 (SIRT3)

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“…However, cancer cells trigger multiple pathways to restore cancer cells from apoptosis (Pentimalli, Grelli, Di Daniele, Melino, & Amelio, 2019). Autophagy, a dynamic intracellular recycling process which eliminates accumulation of damaged proteins or organelles via transport to the lysosomes for degradation (Yuan, Wang, Yang, & Zhang, 2018). Therefore, activation of apoptosis and autophagy could effectively eliminate cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Neferine, an alkaloid from lotus seed embryo targets HeLa and SiHa cervical cancer cells via pro‐oxidant anticancer mechanism

Dasari

Bakthavachalam

Chinnapaka

et al. 2020

Phytotherapy Research

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Apoptosis and autophagy are important processes that control cellular homeostasis and have been highlighted as promising targets for novel anticancer drugs. This study aims to investigate the inhibitory effects and mechanisms of Neferine (Nef), an alkaloid from the lotus seed embryos of Nelumbo nucifera (N. nucifera), as a dual inducer of apoptosis and autophagy through the reactive oxygen species (ROS) activation in cervical cancer cells. Nef and N. nucifera extract suppressed the cell viability of HeLa and SiHa cells in a dose‐dependent manner. Importantly, Nef showed minimal toxicity to normal cells. Furthermore, Nef inhibited anchorage‐independent growth, colony formation and migration ability of cervical cancer cells. Nef induces mitochondrial apoptosis by increasing pro‐apoptotic protein bax, cytochrome‐c, cleaved caspase‐3 and caspase‐9, poly‐ADP ribose polymerase (PARP) cleavage, DNA damage (pH2AX) while downregulating Bcl‐2, procaspase‐3 and procaspase‐9, and TCTP. Of note, apoptotic effect by Nef was significantly attenuated in the presence of N‐acetylcysteine (NAC), suggesting pro‐oxidant activity of this compound. Nef also promoted autophagy induction through increasing beclin‐1, atg‐4, atg‐5 and atg‐12, LC‐3 activation, and P62/SQSTM1 as determined by western blot analysis. Collectively, these results demonstrate that Nef is a potent anticancer compound against cervical cancer cells through inducing apoptosis and autophagic pathway involving ROS.

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The role of ROS-induced autophagy in hepatocellular carcinoma

Cited by 46 publications

References 64 publications

Antiproliferative and Pro-Apoptotic Effect of Uvaol in Human Hepatocarcinoma HepG2 Cells by Affecting G0/G1 Cell Cycle Arrest, ROS Production and AKT/PI3K Signaling Pathway

Antiproliferative and Pro-Apoptotic Effect of Uvaol in Human Hepatocarcinoma HepG2 Cells by Affecting G0/G1 Cell Cycle Arrest, ROS Production and AKT/PI3K Signaling Pathway

Sirtuin3 deficiency exacerbates carbon tetrachloride−induced hepatic injury in mice

Neferine, an alkaloid from lotus seed embryo targets HeLa and SiHa cervical cancer cells via pro‐oxidant anticancer mechanism

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