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المؤلفHadeel, Kheraldine
المؤلفGupta, Ishita
المؤلفAlhussain, Hashim
المؤلفJabeen, Aayesha
المؤلفCyprian, Farhan S.
المؤلفAkhtar, Saghir
المؤلفAl Moustafa, Ala-Eddin
المؤلفRachid, Ousama
تاريخ الإتاحة2021-05-25T06:54:19Z
تاريخ النشر2021-05-07
اسم المنشورComputational and Structural Biotechnology Journal
المعرّفhttp://dx.doi.org/10.1016/j.csbj.2021.05.011
الاقتباسHadeel Kheraldine, Ishita Gupta, Hashim Alhussain, Aayesha Jabeen, Farhan S. Cyprian, Saghir Akhtar, Ala-Eddin Al Moustafa, Ousama Rachid, Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways, Computational and Structural Biotechnology Journal, Volume 19, 2021, Pages 2881-2890, ISSN 2001-0370, https://doi.org/10.1016/j.csbj.2021.05.011.
الرقم المعياري الدولي للكتاب20010370
الرقم المعياري الدولي للكتاب2001-0370
معرّف المصادر الموحدhttps://www.sciencedirect.com/science/article/pii/S2001037021001926
معرّف المصادر الموحدhttp://hdl.handle.net/10576/18454
الملخصHER2-positive breast cancer is one of its most challenging subtypes, forming around 15–25% of the total cases. It is characterized by aggressive behavior and treatment resistance. On the other hand, poly (amidoamine) (PAMAM) dendrimers are widely used in drug delivery systems and gene transfection as carriers. PAMAMs can modulate gene expression and interfere with transactivation of the human epidermal growth factor receptor family members (HER1-4). Nevertheless, the outcome of PAMAMs on HER2-positive breast cancer remains unknown. Thus, in this study, we investigated the anti-cancer effects of different generations of PAMAM dendrimers (G4 and G6) and the outcome of their surface chemistries (cationic, neutral, and anionic) on HER2-positive breast cancer cell lines, SKBR3 and ZR75. Our data showed that PAMAM dendrimers, mainly cationic types, significantly reduce cell viability in a dose-dependent manner. More significantly, PAMAMs induce substantial cell apoptosis, accompanied by the up-regulation of apoptotic markers (Bax, Caspases-3, 8 and 9) in addition to down-regulation of Bcl-2. Moreover, our data pointed out that cationic PAMAMs inhibit colony formation compared to controls and other types of PAMAMs. The molecular pathway analysis of PAMAM exposed cells revealed that PAMAMs enhance JNK1/2/3 expression while blocking ERK1/2, in addition to EGFR1 (HER1) and HER2 activities, which could be the major molecular pathway behind these events. These observed effects were comparable to lapatinib treatment, a clinically used inhibitor of HER1 and 2 receptors phosphorylation. Our findings implicate that PAMAMs may possess important therapeutic effects against HER2-positive breast cancer via JNK1/2/3, ERK1/2, and HER1/2 signalling pathways.
اللغةen
الناشرElsevier
الموضوعPAMAMs
HER2-positive
Breast cancer
Chemoprevention
Apoptosis
العنوانSubstantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways
النوعArticle
الصفحات2881-2890
رقم المجلد19
Open Access user License http://creativecommons.org/licenses/by/4.0/
dc.accessType Open Access


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