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  1. Article: Corrigendum: Carnosol, a natural polyphenol, inhibits migration, metastasis, and tumor growth of breast cancer via a ROS-dependent proteasome degradation of STAT3.

    Alsamri, Halima / Hasasna, Hussain El / Dhaheri, Yusra Al / Eid, Ali H / Attoub, Samir / Iratni, Rabah

    Frontiers in oncology

    2024  Volume 13, Page(s) 1235201

    Abstract: This corrects the article DOI: 10.3389/fonc.2019.00743.]. ...

    Abstract [This corrects the article DOI: 10.3389/fonc.2019.00743.].
    Language English
    Publishing date 2024-02-29
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1235201
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Carnosol Is a Novel Inhibitor of p300 Acetyltransferase in Breast Cancer.

    Alsamri, Halima / Hasasna, Hussain El / Baby, Bincy / Alneyadi, Aysha / Dhaheri, Yusra Al / Ayoub, Mohammed Akli / Eid, Ali H / Vijayan, Ranjit / Iratni, Rabah

    Frontiers in oncology

    2021  Volume 11, Page(s) 664403

    Abstract: Carnosol, a natural polyphenol abundant in edible plants such as sage, rosemary, and oregano, has shown promising anticancer activity against various types of cancers. Nonetheless, very little is known about its molecular mechanism of action or its ... ...

    Abstract Carnosol, a natural polyphenol abundant in edible plants such as sage, rosemary, and oregano, has shown promising anticancer activity against various types of cancers. Nonetheless, very little is known about its molecular mechanism of action or its downstream target(s). We have previously shown that carnosol inhibits cellular proliferation, migration, invasion, and metastasis as well as triggers autophagy and apoptosis in the highly invasive MDA-MB-231 breast cancer cells. Here, we report that carnosol induces histone hypoacetylation in MDA-MB-231 and Hs578T breast cancer cells. We show that, while carnosol does not affect HDACs, it promotes a ROS-dependent proteasome degradation of p300 and PCAF histone acetyl transferases (HATs) without affecting other HATs such as GCN5 and hMOF. Carnosol-induced histone hypoacetylation remains persistent even when p300 and PCAF protein levels were rescued from degradation by (i) the inhibition of the proteasome activity by the proteasome inhibitors MG-132 and bortezomib, and (ii) the inhibition of ROS accumulation by the ROS scavenger, N-acetylcysteine. In addition, we report that, in a cell-free system, carnosol efficiently inhibits histone acetyltransferase activity of recombinant p300 but not that of PCAF or GCN5. Molecular docking studies reveal that carnosol inhibits p300 HAT activity by blocking the entry of the acetyl-CoA binding pocket of the catalytic domain. The superimposition of the docked conformation of the p300 HAT domain in complex with carnosol shows a similar orientation as the p300 structure with acetyl-CoA. Carnosol occupies the region where the pantetheine arm of the acetyl-CoA is bound. This study further confirms carnosol as a promising anti-breast cancer therapeutic compound and identifies it as a novel natural p300 inhibitor that could be added to the existing panel of inhibitors.
    Language English
    Publishing date 2021-05-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2021.664403
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rhus coriaria increases protein ubiquitination, proteasomal degradation and triggers non-canonical Beclin-1-independent autophagy and apoptotic cell death in colon cancer cells.

    Athamneh, Khawlah / Hasasna, Hussain El / Samri, Halima Al / Attoub, Samir / Arafat, Kholoud / Benhalilou, Nehla / Rashedi, Asma Al / Dhaheri, Yusra Al / AbuQamar, Synan / Eid, Ali / Iratni, Rabah

    Scientific reports

    2017  Volume 7, Issue 1, Page(s) 11633

    Abstract: Colorectal cancer is the fourth leading cause of cancer-related deaths worldwide. Here, we investigated the anticancer effect of Rhus coriaria extract (RCE) on HT-29 and Caco-2 human colorectal cancer cells. We found that RCE significantly inhibited the ... ...

    Abstract Colorectal cancer is the fourth leading cause of cancer-related deaths worldwide. Here, we investigated the anticancer effect of Rhus coriaria extract (RCE) on HT-29 and Caco-2 human colorectal cancer cells. We found that RCE significantly inhibited the viability and colony growth of colon cancer cells. Moreover, RCE induced Beclin-1-independent autophagy and subsequent caspase-7-dependent apoptosis. Blocking of autophagy by chloroquine significantly reduced RCE-induced cell death, while blocking of apoptosis had no effect on RCE-induced cell death. Mechanistically, RCE inactivated the AKT/mTOR pathway by promoting the proteasome-dependent degradation of both proteins. Strikingly, we also found that RCE targeted Beclin-1, p53 and procaspase-3 to degradation. Proteasome inhibition by MG-132 not only restored these proteins to level comparable to control cells, but also reduced RCE-induced cell death and blocked the activation of autophagy and apoptosis. The proteasomal degradation of mTOR, which occurred only 3 hours post-RCE treatment was concomitant with an overall increase in the level of ubiquitinated proteins and translated stimulation of proteolysis by the proteasome. Our findings demonstrate that Rhus coriaria possesses strong anti-colon cancer activity through stimulation of proteolysis as well as induction of autophagic and apoptotic cell death, making it a potential and valuable source of novel therapeutic cancer drug.
    MeSH term(s) Animals ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects ; Autophagy/drug effects ; Autophagy/genetics ; Beclin-1/genetics ; Beclin-1/metabolism ; Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Colonic Neoplasms/metabolism ; Disease Models, Animal ; Gene Knockout Techniques ; Humans ; Mice ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis/drug effects ; Rhus/chemistry ; Ubiquitination/drug effects
    Chemical Substances Antineoplastic Agents, Phytogenic ; Beclin-1 ; Plant Extracts ; Caspase 3 (EC 3.4.22.-) ; Caspase 7 (EC 3.4.22.-) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2017-09-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-017-11202-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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