Chemical synthesis and functional characterization of a new class of ceramide analogues as anti-cancer agents

Liu, Qianqian; Li, Xia; Bao, Yong‐Sheng; Lu, Jingxin; Li, Hua; Huang, Zhi‐Zhen; Liu, Feiyan

doi:10.1016/j.bmc.2019.02.030

Cited by 7 publications

(6 citation statements)

References 30 publications

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“…Western blotting. Western blot analysis for the protein was performed according to a previously published protocol (27). The total protein was extracted from the indicated cells using lysis buffer (1X PBS, 900 µl; 2.1 mg/ml Aprotinin, 10 µl; 1 mg/ml Leupeptin, 0.5 µl; 4.9 mg/ml MgCl 2 , 1 µl; 100 mM Sodium Ortho-Vabadate, 10 µl; 10% Triton X-100, 100 µl; and 100 mM PMSF, 10 µl).…”

Section: Colony Formation Assaymentioning

confidence: 99%

Impact of Nischarin on EMT regulators in breast cancer cell lines

Cai

Wang

et al. 2020

Oncol Lett

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Nischarin is an integrin-binding protein, which is well known as a novel tumor suppressor. In breast cancer, Nischarin serves a critical role in breast cancer cell migration and invasion. However, the molecular mechanism underlying the role of Nischarin remains unclear. Recent findings have demonstrated that epithelial-mesenchymal transition (EMT) increases the capacity of cell migration and invasion. As a member of the integrin family, it was hypothesized that Nischarin may regulate cellular processes via various signaling pathways associated with the EMT process. The present study detected the mRNA levels of EMT regulators via reverse transcription-quantitative PCR and related protein levels via western blotting in breast cancer cells, following NISCH-overexpression and-knockdown. The results demonstrated that Nischarin inhibits cell proliferation, migration and invasion in breast cancer cells. Furthermore, when the NISCH gene was overexpressed, the relative mRNA level of E-cadherin was increased, while the relative mRNA levels of several transcription factors, such as Snail, ZEB1, N-cadherin, Slug, Twist1 and vimentin, decreased. When NISCH was silenced, these results were reversed. The present results demonstrated that Nischarin suppresses cell migration and invasion via inhibiting the EMT process.

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Section: Colony Formation Assaymentioning

confidence: 99%

Impact of Nischarin on EMT regulators in breast cancer cell lines

Cai

Wang

et al. 2020

Oncol Lett

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“…Recombinant TRAIL protein was purified as described in the previous article [24]. Ceramide analog 5cc N-((2S,3R)-3-hydroxy-1-oxo-1-(tetradecylamino) butan-2-yl)-2-thiophene carboxamide was synthesized as previously described [23]. DMSO was used to dilute 5cc.…”

Section: Methodsmentioning

confidence: 99%

“…We previously synthesized a new series of ceramide analogs using l -threonine as a starting material. In the screening, most analogs exhibited strong cytotoxicity against different types of human cancer cells including 5cc [23]. Preliminary studies have shown that several ceramide analogs can effectively increase TRAIL-mediated apoptosis in human cancer cells [23].…”

Section: Introductionmentioning

confidence: 99%

“…In the screening, most analogs exhibited strong cytotoxicity against different types of human cancer cells including 5cc [23]. Preliminary studies have shown that several ceramide analogs can effectively increase TRAIL-mediated apoptosis in human cancer cells [23]. We hypothesized that ceramide analog 5cc-targeted blockade of the pro-survival signaling cascade would strongly enhance TRAIL-mediated apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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Ceramide Analog 5cc Overcomes TRAIL Resistance by Enhancing JNK Activation and Repressing XIAP Expression in Metastatic Colon Cancer Cells

Huang¹,

Liu²

2023

Chemotherapy

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Introduction: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to be an effective apoptosis inducer due to its selectivity for tumor cells. However, many cancer cells, especially metastatic cancer cells, often exhibit resistance to TRAIL because their apoptotic pathway is impaired or their pro-survival pathway is overactivated. TRAIL resistance is the main obstacle to current TRAIL therapy. Nowadays, ceramide analogs represent a new class of potential anticancer agents. Therefore, we hypothesized that disrupting pro-survival signaling with ceramide analogs would increase TRAIL-mediated apoptosis. Methods: MTT assay and flow cytometry were conducted to evaluate the synergistic effect of ceramide analog 5cc on TRAIL in metastatic colon cancer cells. Western blot was used to detect signaling proteins affected by 5cc. RNA interference was performed to analyze the effects of specific gene on 5cc-enhanced apoptosis. Results: Ceramide analog 5cc markedly enhanced TRAIL-induced apoptosis evidenced by increased propidium iodide/annexin V double-positive cells and PARP cleavage in SW620 and LS411N cells. At the molecular level, 5cc significantly reduced the expression of anti-apoptotic protein X-linked inhibitor of apoptosis protein (XIAP) through the activation of the c-Jun n-terminal kinase (JNK) pathway which is critically involved in sensitizing tumor cells to TRAIL/5cc combination. JNK-silenced cells exhibited a significant reversal of TRAIL/5cc-mediated apoptosis. Conclusion: Our data demonstrated that ceramide analog 5cc overcomes TRAIL resistance by enhancing JNK activation and repressing XIAP expression in metastatic colon cancer cells.

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“…The oligosaccharides were functionalized with fatty acid and lipidic isocyanides, yielding glycolipids. Thus, this approach can multi-functionalize biomolecules in one spot synthesis, opening possibilities for accessing DDS analogs of anti-cancer glycolipids (Figure 9A) (Pérez-Labrada et al, 2012;Liu et al, 2019).…”

Section: Lipid-lipid and Lipid-oligosaccharide Conjugationmentioning

confidence: 99%

Chemical Conjugation in Drug Delivery Systems

Eras

Castillo²,

Suárez³

et al. 2022

Front. Chem.

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Cancer is one of the diseases with the highest mortality rate. Treatments to mitigate cancer are usually so intense and invasive that they weaken the patient to cure as dangerous as the own disease. From some time ago until today, to reduce resistance generated by the constant administration of the drug and improve its pharmacokinetics, scientists have been developing drug delivery system (DDS) technology. DDS platforms aim to maximize the drugs’ effectiveness by directing them to reach the affected area by the disease and, therefore, reduce the potential side effects. Erythrocytes, antibodies, and nanoparticles have been used as carriers. Eleven antibody–drug conjugates (ADCs) involving covalent linkage has been commercialized as a promising cancer treatment in the last years. This review describes the general features and applications of DDS focused on the covalent conjugation system that binds the antibody carrier to the cytotoxic drug.

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Chemical synthesis and functional characterization of a new class of ceramide analogues as anti-cancer agents

Cited by 7 publications

References 30 publications

Impact of Nischarin on EMT regulators in breast cancer cell lines

Impact of Nischarin on EMT regulators in breast cancer cell lines

Ceramide Analog 5cc Overcomes TRAIL Resistance by Enhancing JNK Activation and Repressing XIAP Expression in Metastatic Colon Cancer Cells

Chemical Conjugation in Drug Delivery Systems

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