Autophagy Inhibition Promotes Gambogic Acid-induced Suppression of Growth and Apoptosis in Glioblastoma Cells

Luo, Guoxuan; Cai, Jun; Lin, Jing-Zhi; Luo, Wei; Luo, Hengshan; Jiang, Yuyang; Zhang, Yong

doi:10.7314/apjcp.2012.13.12.6211

Cited by 32 publications

(20 citation statements)

References 33 publications

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“…Our results show that SSZ significantly inhibits the proliferation of HSC-4 cells. This finding is supported by positive AVO and MDC staining and the conversion of LC3-I to LC3-II, a hallmark of autophagy induction modulated by Atg5-12 conjugate (Ravikumar et al, 2009;Luo et al, 2012). Moreover, SSZ-induced autophagy was found to occur with the involvements of the AKT and ERK pathways.…”

Section: Discussionsupporting

confidence: 64%

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Sulfasalazine Induces Autophagic Cell Death in Oral Cancer Cells via Akt and ERK Pathways

Han¹,

Kim²,

Jeong³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Sulfasalazine (SSZ) is an anti-inflammatory drug that has been used to treat inflammatory bowel disease and rheumatoid arthritis for decades. Recently, some reports have suggested that SSZ also has anti-cancer properties against human tumors. However, little is known about the effects of SSZ on oral cancer. The aim of this study was to investigate the anti-cancer effects of SSZ in oral squamous cell carcinoma (OSCC) cells and to elucidate the mechanisms involved. The authors investigated the anti-proliferative effect of SSZ using the MTT method in HSC-4 cells (an OSCC cell line). Cell cycle analysis, acidic vesicular organelle (AVO) staining, monodansylcadaverine (MDC) staining and Western blotting were also conducted to investigate the cytotoxic mechanism of SSZ. SSZ significantly inhibited the proliferation of HSC-4 cells in a dose-dependent manner. In addition, SSZ induced autophagic cell death, increased microtubule-associated protein 1 light chain (MAP1-LC; also known as LC) 3-II levels, as well as induced punctate AVO and MDC staining, resulted in autophagic cell death. Furthermore, these observations were accompanied by the inhibition of the Akt pathway and the activation of ERK pathway. These results suggest that SSZ promotes autophagic cell death via Akt and ERK pathways and has chemotherapeutic potential for the treatment of oral cancer.

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Section: Discussionsupporting

confidence: 64%

“…Autophagy was initially thought to act in a cytoprotective manner under starvation conditions and in the presence of pathologic infection and immunity (Luo et al, 2012). Under these circumstances, autophagosomes can be formed to degrade damaged microorganelles for energy production or to engulf and remove antigens (Zhou et al, 2012).…”

Section: Lc3-i Lc3-iimentioning

confidence: 99%

Sulfasalazine Induces Autophagic Cell Death in Oral Cancer Cells via Akt and ERK Pathways

Han¹,

Kim²,

Jeong³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Recent studies show that GA can induce the accumulation of ROS in cancer cells contributing to the anti-cancer activity [40], [41], [42], while autophagy can inhibit the therapeutic effect of GA on glioblastoma cells [43]. In this study, we found that GA could promote apoptosis and autophagy in colorectal cancer cells in vitro and in vivo , and inhibition of autophagy enhanced the sensitivity against GA treatment.…”

Section: Introductionsupporting

confidence: 55%

ROS-Mediated Autophagy Induced by Dysregulation of Lipid Metabolism Plays a Protective Role in Colorectal Cancer Cells Treated with Gambogic Acid

Zhang

Yuan

et al. 2014

PLoS ONE

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Gambogic acid (GA), the main active component of gamboge resin, has potent antitumor activity both in vivo and in vitro. However, the underlying molecular mechanisms remain unclear. In this study, we found that GA could initiate autophagy in colorectal cancer cells, and inhibition of the autophagy process accelerated the effect of proliferative inhibition and apoptotic cell death induced by GA, implying a protective role of autophagy. Two-dimensional electrophoresis-based proteomics showed that GA treatment altered the expression of multiple proteins involved in redox signaling and lipid metabolism. Functional studies revealed that GA-induced dysregulation of lipid metabolism could activate 5-lipoxygenase (5-LOX), resulting in intracellular ROS accumulation, followed by inhibition of Akt-mTOR signaling and autophagy initiation. Finally, results using a xenograft model suggested ROS-induced autophagy protect against the antitumor effect of GA. Taken together, these data showed new biological activities of GA against colorectal cancer underlying the protective role of ROS-induced autophagy. This study will provide valuable insights for future studies regarding the anticancer mechanisms of GA.

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“…Treating gastric cancer cell line SGC7901 with autophagy inhibitor, significantly enhanced cisplatin induced apoptosis . Likewise, treating U251 and U87MG glioblastoma cells with autophagy inhibitors substantially enhanced gambogic acid induced apoptosis (Luo et al, 2012).…”

Section: Treating Cancer Cells With Atm Inhibitors and Autophagy Inhimentioning

confidence: 95%

Recently Emerging Signaling Landscape of Ataxia-Telangiectasia Mutated (ATM) Kinase

Farooqı

Attar²,

Arslan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Asian Pac J Cancer Prev, 15 (16), 6485-6488 IntroductionResearch over decades has gradually and sequentially provided near complete resolution of DNA damage signaling and it is now known that DNA damage repair pathway consists of protein network that is highly branched, tightly regulated and well orchestrated. Ataxiatelangiectasia mutated kinase (ATM), ATR and DNAPKcs are members of phosphoinositide-3-kinase-related protein kinase (PIKK) family. It is evident that DNA damage mediated activation of PIKK family members ATM, ATR and DNA-PKcs is further systematically categorized into modes of repair including homologous recombination (HR) and non-Homologous End Joining (NHEJ).Emerging lines of evidence reveal that ATM is a master regulator of DNA damage signaling and gatekeeper of genome integrity. It has lately been shown that ATM-mediated mitotic arrest-deficient protein 1 (Mad1) phosphorylation at Serine 214 induced homodimerization of Mad1 and its heterodimerization with Mad2. These mechanisms were noted to be necessary for chromosomal stability (Yang et al., 2014). Hepatocyte nuclear factor-1 alpha (HNF1α) is also phosphorylated by ATM at Ser249 AbstractResearch over the years has progressively and sequentially provided near complete resolution of regulators of the DNA repair pathways which are so important for cancer prevention. Ataxia-telangiectasia mutated kinase (ATM), a high-molecular-weight PI3K-family kinase has emerged as a master regulator of DNA damage signaling and extensive cross-talk between ATM and downstream proteins forms an interlaced signaling network. There is rapidly growing scientific evidence emphasizing newly emerging paradigms in ATM biology. In this review, we provide latest information regarding how oxidative stress induced activation of ATM can be utilized as a therapeutic target in different cancer cell lines and in xenografted mice. Moreover, crosstalk between autophagy and ATM is also discussed with focus on how autophagy inhibition induces apoptosis in cancer cells.

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Autophagy Inhibition Promotes Gambogic Acid-induced Suppression of Growth and Apoptosis in Glioblastoma Cells

Cited by 32 publications

References 33 publications

Sulfasalazine Induces Autophagic Cell Death in Oral Cancer Cells via Akt and ERK Pathways

Sulfasalazine Induces Autophagic Cell Death in Oral Cancer Cells via Akt and ERK Pathways

ROS-Mediated Autophagy Induced by Dysregulation of Lipid Metabolism Plays a Protective Role in Colorectal Cancer Cells Treated with Gambogic Acid

Recently Emerging Signaling Landscape of Ataxia-Telangiectasia Mutated (ATM) Kinase

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