Bcl‐2 family in non‐small cell lung cancer: its prognostic and therapeutic implications

Sun, Ping; Sasano, Hironobu; Gao, Hongwen

doi:10.1111/pin.12507

Cited by 13 publications

(13 citation statements)

References 63 publications

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“…Overexpression of BAG3 can synergistically act with BCL-2 to induce anti-apoptotic effects and play an important role in the progression of tumors 21. The expression of BCL2 proved to inhibit the process of apoptosis and lots of studies have shown that BCL2 was an important oncogene in the development of lung cancer 22,23. In this study, western blot analysis showed that BAG3 and BCL2 were significantly decreased after silencing FAM111B.…”

Section: Discussionmentioning

confidence: 53%

<p>FAM111B, a direct target of p53, promotes the malignant process of lung adenocarcinoma</p>

Sun¹,

Liu²,

Huang³

et al. 2019

OTT

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Purpose: Lung adenocarcinoma (LUAD) is a main subtype of lung cancer, which is the leading cause of cancer-related deaths. The five-year survival rates of lung cancer patients are still comparatively low. Therefore, potential therapeutic targets are urgently needed to improve the survival of lung cancer patients. In this study, we identified FAM111B as an oncogene and potential therapeutic target for LUAD. Methods: The TCGA database and tissue microarray analysis were used to compare the expression of FAM111B in tumor tissue and normal tissues and evaluate the relationship between FAM111B expression and clinical survival. FAM111B was knocked down and overexpressed to observe whether FAM111B could affect the proliferation, migration, cell cycle, and apoptosis of LUAD cells in vivo and in vitro. Results: FAM111B was highly expressed in tumor tissues compared with normal tissues ( P <0.01). LUAD patients with hyper-expression of FAM111B had a lower recurrence-free survival ( P <0.01) and shorter overall survival ( P <0.01). Knocking down FAM111B inhibited cell proliferation, migration and invasion in vitro and tumor growth in vivo. Silencing FAM111B could arrest LUAD cells at G2/M phase and increase apoptosis. Overexpression of FAM111B promoted the growth of lung cancer cells. FAM111B was identified as a direct target of p53 in existing researches by chip-seq analysis. Bioinformatics analysis predicted that FAM111B could directly bind to BAG3 (BCL2 associated athanogene 3). When FAM111B was down-regulated, both expression of BAG 3 and BCL2 were significantly reduced, whereas decreasing the expression of BAG3 had no effect on FAM111B. Conclusions: Our study indicated that FAM111B might be an oncogene and potential therapeutic target in LUAD which could be involved in the regulation of tumor cells by p53 signaling pathway and play an important role in the process of cell cycle and apoptosis by influencing the expression of BAG3 and BCL2.

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Section: Discussionmentioning

confidence: 53%

<p>FAM111B, a direct target of p53, promotes the malignant process of lung adenocarcinoma</p>

Sun¹,

Liu²,

Huang³

et al. 2019

OTT

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“…In particular, increased expressions of Bcl-2 and Mcl-1 reflect a poor prognosis for many malignancies, including lung cancer [37][38][39]. Not only is their increased expression critical for oncogenesis and cancer progression, but these proteins are also involved in conferring chemotherapeutic drug resistance [35,[40][41][42][43]. Research was performed using Bcl-2 as a target for overcoming chemoresistance through BCL2 gene silencing to improve the clinical outcome in small-cell lung cancer [44].…”

Section: Discussionmentioning

confidence: 99%

Structure–Activity Relationships and Molecular Docking Analysis of Mcl-1 Targeting Renieramycin T Analogues in Patient-derived Lung Cancer Cells

Petsri

Yokoya

Tungsukruthai

et al. 2020

Cancers

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Myeloid cell leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2) proteins are promising targets for cancer therapy. Here, we investigated the structure–activity relationships (SARs) and performed molecular docking analysis of renieramycin T (RT) and its analogues and identified the critical functional groups of Mcl-1 targeting. RT have a potent anti-cancer activity against several lung cancer cells and drug-resistant primary cancer cells. RT mediated apoptosis through Mcl-1 suppression and it also reduced the level of Bcl-2 in primary cells. For SAR study, five analogues of RT were synthesized and tested for their anti-cancer and Mcl-1- and Bcl-2-targeting effects. Only two of them (TM-(–)-18 and TM-(–)-4a) exerted anti-cancer activities with the loss of Mcl-1 and partly reduced Bcl-2, while the other analogues had no such effects. Specific cyanide and benzene ring parts of RT’s structure were identified to be critical for its Mcl-1-targeting activity. Computational molecular docking indicated that RT, TM-(–)-18, and TM-(–)-4a bound to Mcl-1 with high affinity, whereas TM-(–)-45, a compound with a benzene ring but no cyanide for comparison, showed the lowest binding affinity. As Mcl-1 helps cancer cells evading apoptosis, these data encourage further development of RT compounds as well as the design of novel drugs for treating Mcl-1-driven cancers.

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“…The BCL-2 family of proteins, including anti-apoptotic BCL-2 and pro-apoptotic BAX, are critical regulators of the mitochondrial apoptotic pathway and they have been associated with a more aggressive treatment and drug resistance in cancer chemotherapy [43,44,45]. In addition, BCL-2 has been reported as a target gene for many signaling pathways, including the ERK pathway [46,47,48]. The present results indicated that the treatment of cisplatin increased the phosphorylation of ERK proteins, which downregulated the downstream anti-apoptotic BCL-2 protein and upregulated the pro-apoptotic BAX protein in H292 cells.…”

Section: Discussionmentioning

confidence: 99%

5-O-Acetyl-Renieramycin T from Blue Sponge Xestospongia sp. Induces Lung Cancer Stem Cell Apoptosis

et al. 2019

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Lung cancer is one of the most significant cancers as it accounts for almost 1 in 5 cancer deaths worldwide, with an increasing incident rate. Management of the cancer has been shown to frequently fail due to the ability of the cancer cells to resist therapy as well as metastasis. Recent evidence has suggested that the poor response to the current treatment drugs and the ability to undergo metastasis are driven by cancer stem cells (CSCs) within the tumor. The discovery of novel compounds able to suppress CSCs and sensitize the chemotherapeutic response could be beneficial to the improvement of clinical outcomes. Herein, we report for the first time that 5-O-acetyl-renieramycin T isolated from the blue sponge Xestospongia sp. mediated lung cancer cell death via the induction of p53-dependent apoptosis. Importantly, 5-O-acetyl-renieramycin T induced the death of CSCs as represented by the CSC markers CD44 and CD133, while the stem cell transcription factor Nanog was also found to be dramatically decreased in 5-O-acetyl-renieramycin T-treated cells. We also found that such a CSC suppression was due to the ability of the compound to deplete the protein kinase B (AKT) signal. Furthermore, 5-O-acetyl-renieramycin T was able to significantly sensitize cisplatin-mediated apoptosis in the lung cancer cells. Together, the present research findings indicate that this promising compound from the marine sponge is a potential candidate for anti-cancer approaches.

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Bcl‐2 family in non‐small cell lung cancer: its prognostic and therapeutic implications

Cited by 13 publications

References 63 publications

<p>FAM111B, a direct target of p53, promotes the malignant process of lung adenocarcinoma</p>

<p>FAM111B, a direct target of p53, promotes the malignant process of lung adenocarcinoma</p>

Structure–Activity Relationships and Molecular Docking Analysis of Mcl-1 Targeting Renieramycin T Analogues in Patient-derived Lung Cancer Cells

5-O-Acetyl-Renieramycin T from Blue Sponge Xestospongia sp. Induces Lung Cancer Stem Cell Apoptosis

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