Globular adiponectin antagonizes leptin-induced growth of cancer cells by modulating inflammasomes activation: Critical role of HO-1 signaling

Background: Anticancer peptides (ACPs) have received increasing attention as a promising class of novel anticancer agents owing to its potent and rapid cytotoxic properties. In this study, we aim to investigate the effects of cationicity and hydrophobicity in modulating the cytotoxicity of PtxC, a class of ACP from the leafy mistletoe Phoradendron tomentosum against the MDA-MB-231 and Vero cells. Method: We designed a series of four PtxC analogues (PA1 – PA4) by residual substitutions with specific amino acids to introduce the specific charge and hydrophobicity alterations to the analogues. The cytotoxicity strength of the PtxC analogues on MDA-MB-231 and Vero cells were tested by using MTT assay at 24 hours post treatment. Results: PA1, PA2 and PA4 displayed marked increases in cytotoxicity against both MDA-MB-231 and Vero cells and can be ranked in the order of PA2 > PA4 > PA1 > PtxC > PA3. Sequence-activity relationship analyses of the designed analogues showed that an increase in the level of cationicity and hydrophobicity correlated well with the enhanced cytotoxic activity of PtxC analogues. This was observed with PA1 (netC +8) and PA2 (netC +10) in comparison to PtxC (netC +7). Similar finding was observed for PA4 (GRAVY +0.070) in contrast to PtxC (GRAVY -0.339). Three-dimensional modelling predicted a double α-helix structure in PtxC class of ACP. The larger first helix in PA2 and PA4 was suggested to be responsible for the enhanced cytotoxicity observed. Conclusion: The critical role of cationicity and hydrophobicity in enhancing cytotoxicity of PtxC class of ACPs were clearly demonstrated in our study. The current findings could be extrapolated to benefit peptide design strategy in other classes of ACPs toward the discovery of highly potent ACPs against cancer cells as potential novel therapeutic agents.

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Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin

FEBS Open Bio ◽

10.1002/2211-5463.12541 ◽

2018 ◽

Vol 8 (12) ◽

pp. 1964-1976 ◽

Cited By ~ 1

Author(s):

Nirmala Tilija Pun ◽

Amrita Khakurel ◽

Aastha Shrestha ◽

Sang‐Hyun Kim ◽

Pil‐Hoon Park

Keyword(s):

Cell Growth ◽

Cancer Cell ◽

Rna Binding ◽

Binding Protein ◽

Critical Role ◽

Rna Binding Protein ◽

Cancer Cell Growth ◽

Globular Adiponectin

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A critical role of AMPK, and Akt, mTOR and Wnt survival signals for the growth control of colon and liver cancer cells with selenium

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.lb450 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Lee Yun‐Kyoung ◽

Song Yi Park ◽

Won Sup Lee ◽

Young‐Joon Surh ◽

Young‐Min Kim ◽

...

Keyword(s):

Liver Cancer ◽

Cancer Cells ◽

Critical Role ◽

Growth Control ◽

Liver Cancer Cells ◽

Survival Signals

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Paracrine interactions between epithelial cells promote colon cancer growth

10.1101/2020.12.16.423051 ◽

2020 ◽

Author(s):

Guillaume Jacquemin ◽

Annabelle Wurmser ◽

Mathilde Huyghe ◽

Wenjie Sun ◽

Meghan Perkins ◽

...

Keyword(s):

Epithelial Cells ◽

Cancer Cells ◽

Stromal Cells ◽

Critical Role ◽

Essential Factor ◽

Transcriptional Responses ◽

Tumour Formation ◽

Different Types ◽

The Impact

AbstractTumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, we uncovered a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative Yap-associated transcriptional programs in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context. We identified the glycoprotein Thrombospondin-1 (Thbs1) as the essential factor that mediates non-cell autonomous morphological and transcriptional responses. Importantly, Thbs1 is associated with bad prognosis in several human cancers. This study reveals the Thbs1-YAP axis as the mechanistic link mediating paracrine interactions between epithelial cells, promoting tumour formation and progression.

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Critical Role of Endogenous Heme Oxygenase 1 as a Tuner of the Invasive Potential of Prostate Cancer Cells

Molecular Cancer Research ◽

10.1158/1541-7786.mcr-08-0325 ◽

2009 ◽

Vol 7 (11) ◽

pp. 1745-1755 ◽

Cited By ~ 74

Author(s):

Geraldine Gueron ◽

Adriana De Siervi ◽

Mercedes Ferrando ◽

Marcelo Salierno ◽

Paola De Luca ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Heme Oxygenase ◽

Critical Role ◽

Heme Oxygenase 1 ◽

Prostate Cancer Cells ◽

Invasive Potential

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Vimentin filaments drive migratory persistence in polyploidal cancer cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2011912117 ◽

2020 ◽

Vol 117 (43) ◽

pp. 26756-26765

Author(s):

Botai Xuan ◽

Deepraj Ghosh ◽

Joy Jiang ◽

Rachelle Shao ◽

Michelle R. Dawson

Keyword(s):

Cancer Cells ◽

Cancer Progression ◽

Structural Integrity ◽

Single Cell Analysis ◽

Critical Role ◽

Critical Function ◽

Rna Knockdown ◽

Interfering Rna ◽

The Impact

Polyploidal giant cancer cells (PGCCs) are multinucleated chemoresistant cancer cells found in heterogeneous solid tumors. Due in part to their apparent dormancy, the effect of PGCCs on cancer progression has remained largely unstudied. Recent studies have highlighted the critical role of PGCCs as aggressive and chemoresistant cancer cells, as well as their ability to undergo amitotic budding to escape dormancy. Our recent study demonstrated the unique biophysical properties of PGCCs, as well as their unusual migratory persistence. Here we unveil the critical function of vimentin intermediate filaments (VIFs) in maintaining the structural integrity of PGCCs and enhancing their migratory persistence. We performed in-depth single-cell analysis to examine the distribution of VIFs and their role in migratory persistence. We found that PGCCs rely heavily on their uniquely distributed and polarized VIF network to enhance their transition from a jammed to an unjammed state to allow for directional migration. Both the inhibition of VIFs with acrylamide and small interfering RNA knockdown of vimentin significantly decreased PGCC migration and resulted in a loss of PGCC volume. Because PGCCs rely on their VIF network to direct migration and to maintain their enlarged morphology, targeting vimentin or vimentin cross-linking proteins could provide a therapeutic approach to mitigate the impact of these chemoresistant cells in cancer progression and to improve patient outcomes with chemotherapy.

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