Physakengose G induces apoptosis via EGFR/mTOR signaling and inhibits autophagic flux in human osteosarcoma cells

Lin, Hua; Zhang, Chao; Zhang, Hao; Xia, Yuan‐Zheng; Zhang, Chuanyang; Luo, Jie; Yang, Lei; Kong, Ling–Yi

doi:10.1016/j.phymed.2018.03.046

Cited by 21 publications

(13 citation statements)

References 28 publications

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“…Previous studies have shown that the EGFR signal pathway has a vital role in OS progression. Lin et al demonstrated that physakengose G induced apoptosis of OS cells through EGFR/mTOR signaling [ 34 ]. Yuan et al found that MAT2B promotes proliferation of OS cells by targeting the EGFR signaling [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma

Yang

Zhang

et al. 2021

J Exp Clin Cancer Res

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Background Osteosarcoma (OS) is the most common primary bone cancer in adolescents and lung metastasis is the leading cause of death in patients with OS. However, the molecular mechanisms that promote OS growth and metastasis remain unknown. Methods We investigated the expression of myosin light chain kinase family members between metastasis and non-metastasis patients in the TARGET database and ensured that only myosin light chain kinase family member 4 (MYLK4) had higher expression in metastatic osteosarcoma patients. Then we confirmed the results by immunohistochemistry (IHC) and Western blotting (WB) of OS tissues. The effect of MYLK4 on the metastasis and proliferation of OS cells was investigated by wound healing, Transwell and colony-formation assays. Mass spectrum analysis was used to ensure the new binding protein of MYLK4. Tissue microarrays analysis was used to show the correlation between MYLK4 and pEGFR (Y1068). A series of in vivo experiments were conducted to reveal the mechanisms by which MYLK4 modulated the metastasis and proliferation of OS. Results Myosin Light Chain Kinase Family Member 4 (MYLK4) was significantly upregulated in metastatic human OS tissues. Growth and metastasis of OS could be accelerated by MYLK4 overexpression, whereas silencing MYLK4 expression resulted in decreased cell growth and metastasis. Mechanistically, mass spectrum analysis showed that MYLK4 interacted with the epidermal growth factor receptor (EGFR) in osteosarcoma cells and promoted growth and metastasis via the EGFR signaling pathway. Tissue microarrays analysis also showed that MYLK4 expression had a positive correlation with the expression of pEGFR (Y1068). Moreover, the EGFR inhibitor gefitinib could partially reverse the effect of cell proliferation and metastasis caused by MYLK4 overexpression. Importantly, the combination of MYLK4 and EGFR inhibitors had synergistic effects on growth and metastasis of OS in vitro and in vivo. Conclusion Our results indicate that MYLK4 promotes OS growth and metastasis by activating the EGFR signaling pathway and can be a novel therapeutic target for the treatment of OS patients.

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Section: Discussionmentioning

confidence: 99%

MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma

Yang

Zhang

et al. 2021

J Exp Clin Cancer Res

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“…Another previous study suggested that the interaction between transforming growth factor-α and EGFR elicited PI3K and AKT activation, which in turn activated nuclear factor-κB, resulting in the expression of intracellular adhesion molecule 1 and contributing to the migration of human OS cells (22). Physakengose G inhibited cell proliferation and induced apoptosis in human osteosarcoma cells through EGFR phosphorylation and epidermal growth factor-induced activation of downstream signaling molecules, including AKT and mammalian target of rapamycin (23). Another previous study demonstrated that Erk may be a downstream signaling molecule of EGFR in OS (24).…”

Section: Discussionmentioning

confidence: 99%

MAT2B promotes proliferation and inhibits apoptosis in osteosarcoma by targeting epidermal growth factor receptor and proliferating cell nuclear antigen

et al. 2019

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Osteosarcoma (OS) is the most commonly diagnosed bone tumor in young people with poor prognosis. At present, the mechanisms underlying tumorigenesis in OS are not well understood. The methionine adnosyltransferase 2B (MAT2B) gene encodes the regulatory subunit of methionine adenosyltransferase (MAT). Recent studies demonstrated that it is highly expressed in a number of human malignancies; however, is undefined in OS. In the present study, MAT2B expression was investigated in tumor samples and cell lines. In vivo and in vitro, lentivirus-mediated small hairpin RNA was constructed to target the MAT2B gene and examine the role of MAT2B in OS proliferation. Microarray analysis was performed to examine the possible downstream molecular target of MAT2B in OS. MAT2B was markedly increased in OS specimens compared with the normal bone tissues, and it was additionally abundantly expressed in OS cell lines. Inhibition of MAT2B expression caused a marked decrease in proliferation and significant increase in apoptosis. In vivo , MAT2B silencing significantly inhibited OS cell growth. Microarray analysis suggested that epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) may function as downstream targets of MAT2B in OS, as confirmed by reverse transcription-quantitative polymerase chain reaction assays and western blotting. Collectively, these results suggested that MAT2B serves a critical role in the proliferation of OS by regulating EGFR and PCNA and that it may be a potential therapeutic target and prognostic factor of OS.

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“…Unlike the two metabolites from the Physalis genus discussed above, which triggered apoptosis in various cell lines, physakengose G, another new secondary plant metabolite from Physalis alkekengi var. franchetii , had an effect similar to that of chloroquine when administered to osteosarcoma cell lines U-2 OS and HOS cells [ 49 ]. The compound inhibited acidification of lysosomes and rendered them dysfunctional, thereby blocking autophagic degradation and promoting cell death.…”

Section: Anticancer Mechanismsmentioning

confidence: 99%

“…The compound inhibited acidification of lysosomes and rendered them dysfunctional, thereby blocking autophagic degradation and promoting cell death. Inhibition of autophagy was considered potentially therapeutic, at least in a cell line model [ 49 ]. Therefore, the diverse effects that some phytochemicals can have on cancer cells mean that data from such studies need to be interpreted with caution.…”

Section: Anticancer Mechanismsmentioning

confidence: 99%

Anticancer Mechanisms of Bioactive Compounds from Solanaceae: An Update

Nkwe

Lotshwao

Rantong

et al. 2021

Cancers

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Plants continue to provide unlimited pharmacologically active compounds that can treat various illnesses, including cancer. The Solanaceae family, besides providing economically important food plants, such as potatoes and tomatoes, has been exploited extensively in folk medicine, as it provides an array of bioactive compounds. Many studies have demonstrated the anticancer potency of some of the compounds, but the corresponding molecular targets are not well defined. However, advances in molecular cell biology and in silico modelling have made it possible to dissect some of the underlying mechanisms. By reviewing the literature over the last five years, we provide an update on anticancer mechanisms associated with phytochemicals isolated from species in the Solanaceae plant family. These mechanisms are conveniently grouped into cell cycle arrest, transcription regulation, modulation of autophagy, inhibition of signalling pathways, suppression of metabolic enzymes, and membrane disruption. The majority of the bioactive compounds exert their antiproliferative effects by inhibiting diverse signalling pathways, as well as arresting the cell cycle. Furthermore, some of the phytochemicals are effective against more than one cancer type. Therefore, understanding these mechanisms provides paths for future formulation of novel anticancer drugs, as well as highlighting potential areas of research.

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Physakengose G induces apoptosis via EGFR/mTOR signaling and inhibits autophagic flux in human osteosarcoma cells

Cited by 21 publications

References 28 publications

MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma

MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma

MAT2B promotes proliferation and inhibits apoptosis in osteosarcoma by targeting epidermal growth factor receptor and proliferating cell nuclear antigen

Anticancer Mechanisms of Bioactive Compounds from Solanaceae: An Update

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