Targeting UNC-51-like kinase 1 and 2 by lignans to modulate autophagy: possible implications in metastatic colorectal cancer

Sain, Arindam; Kandasamy, Thirukumaran; Naskar, Debdut

doi:10.1007/s11030-022-10399-4

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…Phytoestrogens, particularly those derived from sesame and linseed, act as metastasis inhibitors. The mechanism of action seems to be related to the regulation of autophagy, in particular, dietary lignans inhibit UNC-51-like autophagy activating kinase 1/2 [20]. Sesamin, a phytoestrogen belonging to the lignan family, has been observed to act as a metastasis inhibitor in CRC by blocking angiogenesis [21].…”

Section: Mechanisms Of Action Of Phytoestrogensmentioning

confidence: 99%

Mechanisms of Action of Phytoestrogens and Their Role in Familial Adenomatous Polyposis

Falsetti,

Palmini,

Iantomasi

et al. 2024

Pharmaceutics

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Familial adenomatous polyposis (FAP) is a rare disease characterized by the development of adenomatous polyps in the colon and rectum already in adolescence. If left untreated, patients develop colorectal cancer (CRC) with a 100% probability. To date, the gold standard of FAP management is surgery, which is associated with morbidity and mortality. A chemopreventive agent capable of delaying, preventing and reversing the development of CRC has been sought. Several classes of drugs have been used but to date no chemopreventive drug has been found for the management of this disease. In recent years, the importance of estrogen receptors in FAP and CRC, particularly the β subtype, has emerged. Indeed, the expression of the latter is strongly reduced in adenomatous polyps and CRC and is inversely correlated with the aggressiveness of the disease. Since phytoestrogens have a high affinity for this receptor, they have been suggested for use as chemopreventive agents in FAP and CRC. A combination of phytoestrogens and insoluble fibres has proved particularly effective. In this review, the various mechanisms of action of phytoestrogens were analyzed and the effectiveness of using phytoestrogens as an effective chemopreventive strategy was discussed.

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Section: Mechanisms Of Action Of Phytoestrogensmentioning

confidence: 99%

Mechanisms of Action of Phytoestrogens and Their Role in Familial Adenomatous Polyposis

Falsetti,

Palmini,

Iantomasi

et al. 2024

Pharmaceutics

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“…100 ns of MD simulations were executed via the GROMACS (version 2018.3) package by using the GROMOS96 54A7 force field for the top-ranked docked conformations of the molecular docking (22). MD simulations of the protein-peptide complexes were set up after creating the topology parameters for both proteins and ligands through GROMACS and PRODRG2 servers, respectively (23).…”

Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Olive phenolic compounds, potent tankyrase 1 inhibitor exhibit anti colon cancer effects by blocking Wnt/β-catenin pathway

Sain,

Barman,

Khamrai

et al. 2024

Preprint

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Colon cancer (CC) needs special attention to develop novel targets and therapeutic approaches, as the total number of morbidity and mortality is growing rapidly. Although Olive has been long reported for its anti-CC activities but the mode is not completely understood yet. Here, we targeted tankysare 1 (TNKS), an important mediator of the Wnt/β-catenin pathway, crucial in colon carcinogenesis. Bioinformatics analysis revealed that the mutation and copy number alterations of TNKS is found to be 12% whereas the proteins expression of TNKS is moderate to high in tumor groups vs normal in CC datasets. On the more, TNKS and its positively associated genes are found to be concomitant with several carcinogenesis related biological processes and signaling pathways. Further, three olive phytochemicals (apigenin, luteolin, and quercetin), which were shortlisted by employing filters like drug likeness and toxicity screening, molecular docking and finally molecular dynamics simulations, can target tankyrase 1. These ployphenols demonstrated cytotoxic effect in CC (HT-29) cells either alone or in combination. Further, these compounds successfully reduced β-catenin level and its target genes (CCND1, CDK4, and MYC). Overall, inhibition of the Wnt/β-catenin pathway by targeting tankyrase 1 was revealed as one of the anti-CC mechanisms of olive polyphenols.

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“…The postulated mechanism is based on the regulatory role of Lar, Med, and Pino on the cellular autophagy system that is directly linked with cancer survival and metastasis [ 122 ]. Dietary lignans are able to block UNC-51-like autophagy activating kinase 1/2 (ULK1/2), key regulators of metastatic colorectal cancer [ 123 ]. Surprisingly, Yefei Huang et al discovered that Ses can inhibit metastasis of colorectal cancer by blocking angiogenesis [ 124 ].…”

Section: Anticancer Effects Of Lignansmentioning

confidence: 99%

Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites

Jang

Kim

Cho

2022

IJMS

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Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent a type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans can be further modified into END or ENL by the activities of gut microbiota. Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer. Interestingly, the molecular mechanisms of lignans in these diseases involve the inhibition of inflammatory signals, including the nuclear factor (NF)-κB pathway. Therefore, we summarize the recent in vitro and in vivo studies evaluating the biological effects of various lignans, focusing on their values as effective anti-inflammatory agents.

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Targeting UNC-51-like kinase 1 and 2 by lignans to modulate autophagy: possible implications in metastatic colorectal cancer

Cited by 6 publications

References 42 publications

Mechanisms of Action of Phytoestrogens and Their Role in Familial Adenomatous Polyposis

Mechanisms of Action of Phytoestrogens and Their Role in Familial Adenomatous Polyposis

Olive phenolic compounds, potent tankyrase 1 inhibitor exhibit anti colon cancer effects by blocking Wnt/β-catenin pathway

Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites

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