Marine Carotenoid Fucoxanthin Possesses Anti-Metastasis Activity: Molecular Evidence

Garg, Sukant; Afzal, Sajal; Elwakeel, Ahmed; Sharma, Damini; Radhakrishnan, Navaneethan; Dhanjal, Jaspreet Kaur; Sundar, Durai; Kaul, Sunil C.; Wadhwa, Renu

doi:10.3390/md17060338

Cited by 43 publications

(30 citation statements)

References 50 publications

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“…Mortalin-p53 interaction has been implicated in the deregulation of apoptosis contributing to carcinogenesis [ 15 , 22 , 23 , 40 , 41 ]. In line with this, abrogation of mortalin-p53 complex by synthetic and natural molecules, including MKT-077, Mortaparib, withaferin A, withanone, cucurbitacin B, and fucoxanthin were shown to cause growth arrest and/or apoptosis of cancer cells in in vitro, and cause tumour growth suppression in in vivo assays [ 32 , 42 , 43 , 44 , 45 ].…”

Section: Introductionmentioning

confidence: 92%

Identification and Characterization of MortaparibPlus—A Novel Triazole Derivative That Targets Mortalin-p53 Interaction and Inhibits Cancer-Cell Proliferation by Wild-Type p53-Dependent and -Independent Mechanisms

Sari

Elwakeel

Dhanjal

et al. 2021

Cancers

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p53 has an essential role in suppressing the carcinogenesis process by inducing cell cycle arrest/apoptosis/senescence. Mortalin/GRP75 is a member of the Hsp70 protein family that binds to p53 causing its sequestration in the cell cytoplasm. Hence, p53 cannot translocate to the nucleus to execute its canonical tumour suppression function as a transcription factor. Abrogation of mortalin-p53 interaction and subsequent reactivation of p53’s tumour suppression function has been anticipated as a possible approach in developing a novel cancer therapeutic drug candidate. A chemical library was screened in a high-content screening system to identify potential mortalin-p53 interaction disruptors. By four rounds of visual assays for mortalin and p53, we identified a novel synthetic small-molecule triazole derivative (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole, henceforth named MortaparibPlus). Its activities were validated using multiple bioinformatics and experimental approaches in colorectal cancer cells possessing either wild-type (HCT116) or mutant (DLD-1) p53. Bioinformatics and computational analyses predicted the ability of MortaparibPlus to competitively prevent the interaction of mortalin with p53 as it interacted with the p53 binding site of mortalin. Immunoprecipitation analyses demonstrated the abrogation of mortalin-p53 complex formation in MortaparibPlus-treated cells that showed growth arrest and apoptosis mediated by activation of p21WAF1, or BAX and PUMA signalling, respectively. Furthermore, we demonstrate that MortaparibPlus-induced cytotoxicity to cancer cells is mediated by multiple mechanisms that included the inhibition of PARP1, up-regulation of p73, and also the down-regulation of mortalin and CARF proteins that play critical roles in carcinogenesis. MortaparibPlus is a novel multimodal candidate anticancer drug that warrants further experimental and clinical attention.

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Section: Introductionmentioning

confidence: 92%

Identification and Characterization of MortaparibPlus—A Novel Triazole Derivative That Targets Mortalin-p53 Interaction and Inhibits Cancer-Cell Proliferation by Wild-Type p53-Dependent and -Independent Mechanisms

Sari

Elwakeel

Dhanjal

et al. 2021

Cancers

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“…It induces tumor cell apoptosis by regulating the expression of p53, p21, Fas, PUMA, Bcl-2, and caspase-3/8 and inhibiting the cell cycle. Also, a safe dose of fucoxanthin induces the nuclear translocation of p53 and stimulates its function as a transcriptional activator in cancer cells by causing the loss of mortalin-p53 interaction [ 49 ]. This effect reduces the level of landmark proteins related to cell proliferation, survival, and metastasis of cancer cells.…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Advances in Studies on the Pharmacological Activities of Fucoxanthin

et al. 2020

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Fucoxanthin is a natural carotenoid derived mostly from many species of marine brown algae. It is characterized by small molecular weight, is chemically active, can be easily oxidized, and has diverse biological activities, thus protecting cell components from ROS. Fucoxanthin inhibits the proliferation of a variety of cancer cells, promotes weight loss, acts as an antioxidant and anti-inflammatory agent, interacts with the intestinal flora to protect intestinal health, prevents organ fibrosis, and exerts a multitude of other beneficial effects. Thus, fucoxanthin has a wide range of applications and broad prospects. This review focuses primarily on the latest progress in research on its pharmacological activity and underlying mechanisms.

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“…The antiproliferative effect was stated in vitro among others against the following cell lines: leukemic (HD-60) [24,25], epithelial colorectal adenocarcinoma (Caco-2, DLD-1 and HT-29) [26], prostate cancer (PC-3, DU-145, LNCaP) [27,28,29], urinary bladder cancer (EJ-1) [30], osteosarcoma (Saos-2, MNNG/HOS and 143B) [31], breast cancer (MDA-MB-231) [32], non-small-cell lung cancer (NSCLC) [33], and gastric adenocarcinoma (MGC-803) [34]. Other studies presented that fucoxanthin acted preventively against cancer exerting the antiangiogenic, antilymphangiogenic, and antimetastatic effects [32,35,36].…”

Section: Introductionmentioning

confidence: 99%

Fucoxanthin—An Antibacterial Carotenoid

2019

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Fucoxanthin is a carotenoid produced by brown algae and diatoms. This compound has several biological properties such as antioxidant, anti-obesity, anti-diabetic, anticancer, and antimicrobial activities. Unfortunately, until now the latter effect has been poorly confirmed. The aim of this study was an evaluation of fucoxanthin activity against 20 bacterial species. Antimicrobial effect of fucoxanthin was determined by using the agar disc-diffusion and micro-dilution methods. The studied carotenoid acted against 13 bacteria growing in aerobic conditions. It was observed to have a significantly stronger impact on Gram-positive than Gram-negative bacteria. Mean zones of growth inhibition (ZOIs) for Gram-positive bacteria ranged between 9.0 and 12.2 mm, while for Gram-negative were from 7.2 to 10.2 mm. According to the agar disc-diffusion method, the highest activity of fucoxanthin was exhibited against Streptococcus agalactiae (mean ZOI 12.2 mm), Staphylococcus epidermidis (mean ZOI 11.2 mm), and Staphylococcus aureus (mean ZOI 11.0 mm), and in the microdilution test towards Streptococcus agalactiae with the minimal inhibitory concentration (MIC) of 62.5 µg/mL. On the other hand, fucoxanthin was not active against strict anaerobic bacteria.

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Marine Carotenoid Fucoxanthin Possesses Anti-Metastasis Activity: Molecular Evidence

Cited by 43 publications

References 50 publications

Identification and Characterization of MortaparibPlus—A Novel Triazole Derivative That Targets Mortalin-p53 Interaction and Inhibits Cancer-Cell Proliferation by Wild-Type p53-Dependent and -Independent Mechanisms

Identification and Characterization of MortaparibPlus—A Novel Triazole Derivative That Targets Mortalin-p53 Interaction and Inhibits Cancer-Cell Proliferation by Wild-Type p53-Dependent and -Independent Mechanisms

Advances in Studies on the Pharmacological Activities of Fucoxanthin

Fucoxanthin—An Antibacterial Carotenoid

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