Effect of bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 on cell cycle arrest, apoptotic and autophagic pathway in triple-negative breast adenocarcinoma MDA-MB-231 cells: An in vitro study

Carnosol, a phenolic diterpene, is one of the effective anticancer agents naturally occurring in rosemary, sage, parsley, and oregano. The chemoresistance problem increased with the routinely used chemotherapy. Therefore, the efforts to find a substitute with safe and low cost have become crucial worldwide. The current study attempts to inspect the anticancer molecular mechanisms of Carnosol on modulating up- and down- regulation of multiple genetic carcinogenesis pathways. The cytotoxicity of Carnosol on Hela cells was evaluated by MTS assay. Flow cytometry was used to assess apoptosis and cell cycle arrest. The apoptotic morphological changes were obvious by dual apoptosis assay. The differential gene expression after treatment with Carnosol was investigated by qRT-PCR. Up to 80% of the treated cells with Carnosol IC50 underwent apoptosis. Apoptosis together with cell cycle arrest in G0/G1 phase were induced significantly after treatment with Carnosol IC50. Fifteen out of nineteen genes studied were found to be remarkably up- or down- regulated after treatment with Carnosol. Six up-regulated genes (EREG, FOS-2, ID2, CRYAB, DUSP5, and TICAM2) and nine down-regulated genes (FN1, KRAS2, CCNB1-1, FEN1, MCM4, MCM5, GTSE1, CXCL1, and RALA) were recorded. These genes are candidates for future research for elucidating anticancer molecular targeted therapies, cancerous signaling and cancer development pathways in cervical cancer; moreover, elucidating the role of apoptosis, inflammation, cell proliferation, and cell differentiation in the development of cervical cancer.

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W436, a novel SMART derivative, exhibits anti‐hepatocarcinoma activity by inducing apoptosis and G2/M cell cycle arrest in vitro and in vivo and induces protective autophagy

Journal of Biochemical and Molecular Toxicology ◽

10.1002/jbt.22831 ◽

2021 ◽

Author(s):

Shuai Man ◽

Zhuzhu Wu ◽

Rui Sun ◽

Qi Guan ◽

Zengqiang Li ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

M Cell ◽

Cycle Arrest

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Delivery of miR-381-3p Mimic by Mesenchymal Stem Cell-Derived Exosomes Inhibits Triple Negative Breast Cancer Aggressiveness; an In Vitro Study

Stem Cell Reviews and Reports ◽

10.1007/s12015-020-10089-4 ◽

2021 ◽

Author(s):

Samaneh Shojaei ◽

Seyed Mahmoud Hashemi ◽

Hossein Ghanbarian ◽

Kazem Sharifi ◽

Mohammad Salehi ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

In Vitro Study ◽

Vitro Study ◽

Cancer Aggressiveness

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HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7

Virology Journal ◽

10.1186/s12985-021-01514-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Xiaohong Zhou ◽

Christina Monnie ◽

Maria DeLucia ◽

Jinwoo Ahn

Keyword(s):

Cell Cycle ◽

Dna Repair ◽

Cell Cycle Arrest ◽

Histone Deacetylase ◽

E3 Ligase ◽

Cycle Arrest ◽

Wide Range ◽

In Vitro Reconstitution ◽

Hiv 1

Abstract Background Vpr is a virion-associated protein that is encoded by lentiviruses and serves to counteract intrinsic immunity factors that restrict infection. HIV-1 Vpr mediates proteasome-dependent degradation of several DNA repair/modification proteins. Mechanistically, Vpr directly recruits cellular targets onto DCAF1, a substrate receptor of Cullin 4 RING E3 ubiquitin ligase (CRL4) for poly-ubiquitination. Further, Vpr can mediate poly-ubiquitination of DCAF1-interacting proteins by the CRL4. Because Vpr-mediated degradation of its known targets can not explain the primary cell-cycle arrest phenotype that Vpr expression induces, we surveyed the literature for DNA-repair-associated proteins that interact with the CRL4-DCAF1. One such protein is SIRT7, a deacetylase of histone 3 that belongs to the Sirtuin family and regulates a wide range of cellular processes. We wondered whether Vpr can mediate degradation of SIRT7 via the CRL4-DCAF1. Methods HEK293T cells were transfected with cocktails of plasmids expressing DCAF1, DDB1, SIRT7 and Vpr. Ectopic and endogeneous levels of SIRT7 were monitered by immunoblotting and protein–protein interactions were assessed by immunoprecipitation. For in vitro reconstitution assays, recombinant CRL4-DCAF1-Vpr complexes and SIRT7 were prepared and poly-ubiqutination of SIRT7 was monitored with immunoblotting. Results We demonstrate SIRT7 polyubiquitination and degradation upon Vpr expression. Specifically, SIRT7 is shown to interact with the CRL4-DCAF1 complex, and expression of Vpr in HEK293T cells results in SIRT7 degradation, which is partially rescued by CRL inhibitor MNL4924 and proteasome inhibitor MG132. Further, in vitro reconstitution assays show that Vpr induces poly-ubiquitination of SIRT7 by the CRL4-DCAF1. Importantly, we find that Vpr from several different HIV-1 strains, but not HIV-2 strains, mediates SIRT7 poly-ubiquitination in the reconstitution assay and degradation in cells. Finally, we show that SIRT7 degradation by Vpr is independent of the known, distinctive phenotype of Vpr-induced cell cycle arrest at the G2 phase, Conclusions Targeting histone deacetylase SIRT7 for degradation is a conserved feature of HIV-1 Vpr. Altogether, our findings reveal that HIV-1 Vpr mediates down-regulation of SIRT7 by a mechanism that does not involve novel target recruitment to the CRL4-DCAF1 but instead involves regulation of the E3 ligase activity.

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