Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways
HER2-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 a...
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2021
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| Online Access: | http://dx.doi.org/10.1016/j.csbj.2021.05.011 https://www.sciencedirect.com/science/article/pii/S2001037021001926 http://hdl.handle.net/10576/18454 |
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| _version_ | 1857415084521816064 |
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| author | Hadeel, Kheraldine |
| author2 | Gupta, Ishita Alhussain, Hashim Jabeen, Aayesha Cyprian, Farhan S. Akhtar, Saghir Al Moustafa, Ala-Eddin Rachid, Ousama |
| author2_role | author author author author author author author |
| author_facet | Hadeel, Kheraldine Gupta, Ishita Alhussain, Hashim Jabeen, Aayesha Cyprian, Farhan S. Akhtar, Saghir Al Moustafa, Ala-Eddin Rachid, Ousama |
| author_role | author |
| dc.creator.none.fl_str_mv | Hadeel, Kheraldine Gupta, Ishita Alhussain, Hashim Jabeen, Aayesha Cyprian, Farhan S. Akhtar, Saghir Al Moustafa, Ala-Eddin Rachid, Ousama |
| dc.date.none.fl_str_mv | 2021-05-25T06:54:19Z 2021-05-07 |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://dx.doi.org/10.1016/j.csbj.2021.05.011 Hadeel 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. 20010370 2001-0370 https://www.sciencedirect.com/science/article/pii/S2001037021001926 http://hdl.handle.net/10576/18454 2881-2890 19 |
| dc.language.none.fl_str_mv | en |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | PAMAMs HER2-positive Breast cancer Chemoprevention Apoptosis |
| dc.title.none.fl_str_mv | Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | HER2-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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | qu_0f9ef31d646bc43b317232795da4884d |
| identifier_str_mv | Hadeel 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. 20010370 2001-0370 2881-2890 19 |
| language_invalid_str_mv | en |
| network_acronym_str | qu |
| network_name_str | Qatar University repository |
| oai_identifier_str | oai:qspace.qu.edu.qa:10576/18454 |
| publishDate | 2021 |
| publisher.none.fl_str_mv | Elsevier |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| spelling | Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathwaysHadeel, KheraldineGupta, IshitaAlhussain, HashimJabeen, AayeshaCyprian, Farhan S.Akhtar, SaghirAl Moustafa, Ala-EddinRachid, OusamaPAMAMsHER2-positiveBreast cancerChemopreventionApoptosisHER2-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.Elsevier2021-05-25T06:54:19Z2021-05-07Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.csbj.2021.05.011Hadeel 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.2021.05.011.200103702001-0370https://www.sciencedirect.com/science/article/pii/S2001037021001926http://hdl.handle.net/10576/184542881-289019enhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:qspace.qu.edu.qa:10576/184542024-07-23T11:23:38Z |
| spellingShingle | Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways Hadeel, Kheraldine PAMAMs HER2-positive Breast cancer Chemoprevention Apoptosis |
| status_str | publishedVersion |
| title | Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways |
| title_full | Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways |
| title_fullStr | Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways |
| title_full_unstemmed | Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways |
| title_short | Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways |
| title_sort | Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways |
| topic | PAMAMs HER2-positive Breast cancer Chemoprevention Apoptosis |
| url | http://dx.doi.org/10.1016/j.csbj.2021.05.011 https://www.sciencedirect.com/science/article/pii/S2001037021001926 http://hdl.handle.net/10576/18454 |