Larotrectinib induces autophagic cell death through AMPK/mTOR signalling in colon cancer

Kong, Wencheng; Zhu, Hangzhang; Zheng, Sixing; Yin, Guowen; Shan, Yuqiang; Liu, Xinchun; Ying, Rongchao; Zhu, Hong; Ma, Shenglin

doi:10.1111/jcmm.17530

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…Although various anticancer drugs have been developed to treat lung cancer, new therapies are needed due to their many side effects. Recently, many studies have investigated anticancer effects through autophagy activity [54,55].…”

Section: Discussionmentioning

confidence: 99%

JI017 Induces Cell Autophagy and Apoptosis via Elevated Levels of Reactive Oxygen Species in Human Lung Cancer Cells

Kim

Choi

et al. 2023

IJMS

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Lung cancer is one of the most common malignant tumors and a leading cause of cancer-related death in the worldwide. Various anticancer drugs, such as cisplatin and pemetrexed, have been developed for lung cancer treatment but due their drug resistance and side effects, novel treatments need to be developed. In this study, the efficacy of the natural drug JI017, which is known to have few side effects, was tested in lung cancer cells. JI017 inhibited A549, H460, and H1299 cell proliferation. JI017 induced apoptosis, regulated apoptotic molecules, and inhibited colony formation. Additionally, JI017 increased intracellular ROS generation. JI017 downregulated PI3K, AKT, and mTOR expression. JI017 increased the cytosolic accumulation of LC3. We found that JI017 promoted apoptosis through ROS-induced autophagy. Additionally, the xenograft tumor size was smaller in JI017-treated mice. We found that JI017 treatment increased MDA concentrations, decreased Ki-67 protein levels, and increased cleaved caspase-3 and LC3 levels in vivo. JI017 decreased cell proliferation and increased apoptosis by inducing autophagy signaling in H460 and H1299 lung cancer cells. Targeting JI017 and autophagy signaling could be useful in lung cancer treatment.

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Section: Discussionmentioning

confidence: 99%

JI017 Induces Cell Autophagy and Apoptosis via Elevated Levels of Reactive Oxygen Species in Human Lung Cancer Cells

Kim

Choi

et al. 2023

IJMS

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“…Autophagy is a process that regulates cancer survival during stress ( 52 ). Several studies have suggested that autophagy induction inhibits tumor initiation and progression ( 53 , 54 ). Therefore, whether the inhibitory effect of MSpf treatment on cell proliferation was due to induction of autophagy was examined.…”

Section: Discussionmentioning

confidence: 99%

Protein components of maple syrup as a potential resource for the development of novel anti‑colorectal cancer drugs

Yamamoto,

Shiburo,

Moriyama

et al. 2023

Oncol Rep

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Maple syrup is a natural sweetener consumed worldwide. Active ingredients of maple syrup possess antitumor effects; however, these ingredients are phenolic compounds. The present study aimed to investigate components other than phenolic compounds that may have antitumor effects against colorectal cancer (CRC). Cell proliferation assays demonstrated that treatment with the more than 10,000 molecular weight fraction significantly inhibited viability in DLD-1 cells. Therefore, we hypothesized that the protein components of maple syrup may be the active ingredients in maple syrup. We obtained protein components from maple syrup by ammonium sulfate precipitation, and treatment with the protein fraction of maple syrup (MSpf) was found to exhibit a potential antitumor effect. MSpf-treated DLD-1 colon adenocarcinoma cells exhibited significantly decreased proliferation, migration and invasion. In addition, upregulation of LC3A and E-cadherin and downregulation of MMP-9 expression levels were observed following MSpf treatment. Investigation of the components of MSpf suggested that it was primarily formed of advanced glycation end products (AGEs). Therefore, whether AGEs in MSpf affected the STAT3 pathway through the binding to its receptor, receptor of AGE (RAGE), was assessed. MSpf treatment was associated with decreased RAGE expression and STAT3 phosphorylation. Finally, to determine whether autophagy contributed to the inhibitory effect of cell proliferation following MSpf treatment, the effect of MSpf treatment on autophagy induction following bafilomycin A1 treatment, a specific autophagy inhibitor, was assessed. The inhibitory effect of MSpf treatment on cell proliferation was enhanced through the inhibition of autophagy by bafilomycin A1 treatment. These results suggested that AGEs in MSpf suppressed cell proliferation and epithelial-mesenchymal transition through inhibition of the STAT3 signaling pathway through decreased RAGE expression. Therefore, AGEs in MSpf may be potential compounds for the development of antitumor drugs for the treatment of CRC with fewer adverse effects compared with existing antitumor drugs.

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“…Further studies found that MTOR signaling dependent mitochondrial dysfunction promotes colorectal cancer cell death[ 77 ]. Regulation of the Beclin1/Beclin2 signaling pathway may be the key to inducing autophagic death of colorectal cancer cells[ 78 - 80 ]. In addition, a study on the mechanism of lipopolysaccharide-induced injury in the colon adenoma cell lines Caco-2 and HT-29 showed that autophagic flow was blocked at the autolysosome stage in vitro and in vivo [ 81 ].…”

Section: Autophagy and Gi Diseasesmentioning

confidence: 99%

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

Chang,

Li,

Liu

et al. 2024

World J Gastroenterol

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Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes. Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation. A large number of studies have shown that autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal (GI) cells. However, the role of autophagy in GI diseases remains controversial. This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases, in order to provide new ideas for their diagnosis and treatment.

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Larotrectinib induces autophagic cell death through AMPK/mTOR signalling in colon cancer

Cited by 9 publications

References 33 publications

JI017 Induces Cell Autophagy and Apoptosis via Elevated Levels of Reactive Oxygen Species in Human Lung Cancer Cells

JI017 Induces Cell Autophagy and Apoptosis via Elevated Levels of Reactive Oxygen Species in Human Lung Cancer Cells

Protein components of maple syrup as a potential resource for the development of novel anti‑colorectal cancer drugs

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

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