Autophagy dysfunctions associated with cancer cells and their therapeutic implications

Udristioiu, Aurelian; Nica-Badea, Delia

doi:10.1016/j.biopha.2019.108892

Cited by 42 publications

(43 citation statements)

References 81 publications

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“…Our data showed that NOD2 significantly inhibited mTORC1 pathway through its regulation of AMPK pathway, which finally led to autophagy-mediated apoptosis of HCC cells. Autophagy is a cellular self-degradation process in response to stress, and it has been extensively studied in recent years 41,42 . Though both pro-survival and pro-apoptosis role of autophagy have been reported in cancer 43 , it is recognized in recent years that the development of HCC is mainly attributed to deficiency of autophagy of the hepatic parenchymal cells 44 .…”

Section: Discussionmentioning

confidence: 99%

NOD2 inhibits tumorigenesis and increases chemosensitivity of hepatocellular carcinoma by targeting AMPK pathway

Qiu

Sun

et al. 2020

Cell Death Dis

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Nucleotide binding oligomerization domain 2 (NOD2) is a recognized innate immune sensor which can initiate potent immune response against pathogens. Many innate immune sensors have been reported to be of great importance in carcinogenesis. However, the role of NOD2 in cancer is not well understood. Here we investigated the role of NOD2 in the development of hepatocellular carcinoma (HCC). We demonstrated that NOD2 deficiency promoted hepatocarcinogenesis in N-nitrosodiethylamine (DEN)/carbon tetrachloride (CCl 4) induced HCC mice model and xenograft tumor model. In vitro investigation showed that NOD2 acted as a tumor suppressor and inhibited proliferation, colony formation and invasion of HCC cells. Clinical investigation showed that NOD2 expression was completely lost or significantly downregulated in clinical HCC tissues, and loss of NOD2 expression was significantly correlated with advanced disease stages. Further investigation showed that NOD2 exerted its anti-tumor effect through activating adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, and NOD2 significantly enhanced the sensitivity of HCC cells to sorafenib, lenvatinib and 5-FU treatment through activating AMPK pathway induced apoptosis. Moreover, we demonstrated that NOD2 activated AMPK pathway by directly binding with AMPKα-LKB1 complex, which led to autophagy-mediated apoptosis of HCC cells. Altogether, this study showed that NOD2 acted as a tumor suppressor as well as a chemotherapeutic regulator in HCC cells by directly activating AMPK pathway, which indicated a potential therapeutic strategy for HCC treatment by upregulating NOD2-AMPK signaling axis.

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Section: Discussionmentioning

confidence: 99%

NOD2 inhibits tumorigenesis and increases chemosensitivity of hepatocellular carcinoma by targeting AMPK pathway

Qiu

Sun

et al. 2020

Cell Death Dis

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“…Previous studies have revealed that autophagy enhancers can be used as potential treatment strategies for cancer in precancerous lesions ( 37 , 38 ). In advanced cancer, intervening in autophagy has been suggested as one of the effective measures for cancer treatment ( 39 , 40 ). Resveratrol has been revealed to inhibit the proliferation of A549 lung cancer cells and to promote cell death by an autophagic mechanism ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Matrine exerts anti‑breast cancer activity by mediating apoptosis and protective autophagy via the AKT/mTOR pathway in MCF‑7 cells

Jinwen

Song

et al. 2020

Mol Med Rep

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Matrine, a major alkaloid isolated from the traditional chinese herb Sophora flavescens, has been used clinically to treat breast cancer in china. However, the effects of matrine on apoptosis and autophagy in breast cancer cells remain unclear. in the present study, the anti-breast cancer capacity of matrine was evaluated and its role in regulating apoptosis and autophagy in vitro was investigated. Matrine significantly inhibited the growth of McF-7 cells. in addition, Hoechst 33342 staining and annexin V/propidium iodide staining demonstrated that incubation with matrine induced apoptosis in McF-7 cells. Furthermore, matrine induced autophagy in McF-7 cells, manifesting as an accumulation of light chain 3 ii and downregulation of p62. additionally, matrine suppressed aKT and mammalian target of rapamycin (mTor) phosphorylation, indicating that the aKT/mTor pathway is involved in matrine-induced apoptosis and autophagy. overall, the results of the present study indicated that matrine possesses anti-breast cancer activity by providing protective autophagy via inhibition of the aKT/mTor pathway. These findings indicated that matrine may be a promising candidate for drug development targeting breast cancer.

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“…Autophagy usually helps cancer cells to cope with the shortage of nutrients and with the hypoxic conditions in which they are forced to survive. The modulation of autophagy may play dual roles in tumor suppression and promotion [2, 3]. Its induction is generally considered a valid option in cancer prevention [4], particularly because through a selective form of autophagy, that is the mitophagy, cells ride out of damaged mitochondria, the main producers of reactive oxygen species (ROS) that cause DNA mutations [5].…”

Section: Introductionmentioning

confidence: 99%

“…Its induction is generally considered a valid option in cancer prevention [4], particularly because through a selective form of autophagy, that is the mitophagy, cells ride out of damaged mitochondria, the main producers of reactive oxygen species (ROS) that cause DNA mutations [5]. Autophagy modulators have been used as new anticancer strategy [3, 6], although how to manipulate autophagy to improve the treatment of established cancers is still not clear. Recently, a role of autophagy in the regulation the function of the cells present in the tumor microenvironment such as cancer-associated fibroblasts and immune cells has been highlighted, making the issue of autophagy manipulation even more challenging [7, 8].…”

Section: Introductionmentioning

confidence: 99%

Autophagy manipulation as a strategy for efficient anticancer therapies: possible consequences

Cirone

Montani

Granato

et al. 2019

J Exp Clin Cancer Res

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Autophagy is a catabolic process whose activation may help cancer cells to adapt to cellular stress although, in some instances, it can induce cell death. Autophagy stimulation or inhibition has been considered an opportunity to treat cancer, especially in combination with anticancer therapies, although autophagy manipulation may be viewed as controversial. Thus, whether to induce or to inhibit autophagy may be the best option in the different cancer patients is still matter of debate. Her we will recapitulate the possible advantages or disadvantages of manipulating autophagy in cancer, not only with the aim to obtain cancer cell death and disable oncogenes, but also to evaluate its interplay with the immune response which is fundamental for the success of anticancer therapies.

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Autophagy dysfunctions associated with cancer cells and their therapeutic implications

Cited by 42 publications

References 81 publications

NOD2 inhibits tumorigenesis and increases chemosensitivity of hepatocellular carcinoma by targeting AMPK pathway

NOD2 inhibits tumorigenesis and increases chemosensitivity of hepatocellular carcinoma by targeting AMPK pathway

Matrine exerts anti‑breast cancer activity by mediating apoptosis and protective autophagy via the AKT/mTOR pathway in MCF‑7 cells

Autophagy manipulation as a strategy for efficient anticancer therapies: possible consequences

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