Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathways

<p dir="ltr">Squamous cell carcinoma is a frequent skin cancer still demanding to understand the underlying mechanisms for better clinical outcomes. Pristimerin, a natural quinonemethide triterpenoid, has shown promising therapeutic outcome due to its anti-cancer activity and multi-t...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Maha Al-Tamimi (17280550) (author)
مؤلفون آخرون: Abdul Q. Khan (14153247) (author), Rasheeda Anver (17346850) (author), Fareed Ahmad (134672) (author), Jericha M Mateo (17346853) (author), Syed Shadab Raza (5775911) (author), Majid Alam (14158959) (author), Joerg Buddenkotte (6293584) (author), Martin Steinhoff (5340194) (author), Shahab Uddin (154400) (author)
منشور في: 2022
الموضوعات:
الوسوم: إضافة وسم
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author Maha Al-Tamimi (17280550)
author2 Abdul Q. Khan (14153247)
Rasheeda Anver (17346850)
Fareed Ahmad (134672)
Jericha M Mateo (17346853)
Syed Shadab Raza (5775911)
Majid Alam (14158959)
Joerg Buddenkotte (6293584)
Martin Steinhoff (5340194)
Shahab Uddin (154400)
author2_role author
author
author
author
author
author
author
author
author
author_facet Maha Al-Tamimi (17280550)
Abdul Q. Khan (14153247)
Rasheeda Anver (17346850)
Fareed Ahmad (134672)
Jericha M Mateo (17346853)
Syed Shadab Raza (5775911)
Majid Alam (14158959)
Joerg Buddenkotte (6293584)
Martin Steinhoff (5340194)
Shahab Uddin (154400)
author_role author
dc.creator.none.fl_str_mv Maha Al-Tamimi (17280550)
Abdul Q. Khan (14153247)
Rasheeda Anver (17346850)
Fareed Ahmad (134672)
Jericha M Mateo (17346853)
Syed Shadab Raza (5775911)
Majid Alam (14158959)
Joerg Buddenkotte (6293584)
Martin Steinhoff (5340194)
Shahab Uddin (154400)
dc.date.none.fl_str_mv 2022-12-01T00:00:00Z
dc.identifier.none.fl_str_mv 10.1016/j.biopha.2022.113950
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Pristimerin_mediated_anticancer_effects_and_sensitization_of_human_skin_cancer_cells_through_modulation_of_MAPK_signaling_pathways/24516421
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Pristimerin
Squamous cell carcinoma
Signal transduction
Autophagy
Apoptosis
JNK
dc.title.none.fl_str_mv Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathways
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Squamous cell carcinoma is a frequent skin cancer still demanding to understand the underlying mechanisms for better clinical outcomes. Pristimerin, a natural quinonemethide triterpenoid, has shown promising therapeutic outcome due to its anti-cancer activity and multi-targeting potential. We explored the underlying mechanisms of pristimerin-induced programmed cell death of primary (A431) and metastatic (A388) cutaneous squamous cell carcinoma (cSCC) cells. Our results show that pristimerin inhibits growth and proliferation of cSCC through JNK activation. Moreover, pristimerin causes cell cycle arrest and induces cell death via apoptosis and autophagy. Interestingly, use of apoptosis (z-VAD-FMK) and autophagy (3-methyladenine) inhibitors confirmed vital role of programmed cell death in pristimerin-mediated anti-cancer actions. JNK inhibitor, SP600125, also mitigated pristimerin-induced apoptotic and autophagic actions. Moreover, pristimerin-mediated anti-cancer activity acts by generating reactive oxygen species (ROS) thereby inducing JNK signaling. Use of N-acetyl cystine (NAC), a universal ROS scavenger, significantly reversed pristimerin-induced programmed cell death through downregulation of JNK. Pristimerin sensitized skin cancer cells to conventional anticancer drugs cisplatin, azacytidine and doxorubicin through JNK activation, as confirmed by SP600125. Our results indicate that pristimerin mediates programmed cell death and sensitized skin cancer cells to conventional anti-cancer drugs via ROS-mediated JNK activation.</p><h2>Other Information</h2><p dir="ltr">Published in: Biomedicine & Pharmacotherapy<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.biopha.2022.113950" target="_blank">https://dx.doi.org/10.1016/j.biopha.2022.113950</a></p>
eu_rights_str_mv openAccess
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identifier_str_mv 10.1016/j.biopha.2022.113950
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/24516421
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spelling Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathwaysMaha Al-Tamimi (17280550)Abdul Q. Khan (14153247)Rasheeda Anver (17346850)Fareed Ahmad (134672)Jericha M Mateo (17346853)Syed Shadab Raza (5775911)Majid Alam (14158959)Joerg Buddenkotte (6293584)Martin Steinhoff (5340194)Shahab Uddin (154400)Biomedical and clinical sciencesClinical sciencesOncology and carcinogenesisPharmacology and pharmaceutical sciencesPristimerinSquamous cell carcinomaSignal transductionAutophagyApoptosisJNK<p dir="ltr">Squamous cell carcinoma is a frequent skin cancer still demanding to understand the underlying mechanisms for better clinical outcomes. Pristimerin, a natural quinonemethide triterpenoid, has shown promising therapeutic outcome due to its anti-cancer activity and multi-targeting potential. We explored the underlying mechanisms of pristimerin-induced programmed cell death of primary (A431) and metastatic (A388) cutaneous squamous cell carcinoma (cSCC) cells. Our results show that pristimerin inhibits growth and proliferation of cSCC through JNK activation. Moreover, pristimerin causes cell cycle arrest and induces cell death via apoptosis and autophagy. Interestingly, use of apoptosis (z-VAD-FMK) and autophagy (3-methyladenine) inhibitors confirmed vital role of programmed cell death in pristimerin-mediated anti-cancer actions. JNK inhibitor, SP600125, also mitigated pristimerin-induced apoptotic and autophagic actions. Moreover, pristimerin-mediated anti-cancer activity acts by generating reactive oxygen species (ROS) thereby inducing JNK signaling. Use of N-acetyl cystine (NAC), a universal ROS scavenger, significantly reversed pristimerin-induced programmed cell death through downregulation of JNK. Pristimerin sensitized skin cancer cells to conventional anticancer drugs cisplatin, azacytidine and doxorubicin through JNK activation, as confirmed by SP600125. Our results indicate that pristimerin mediates programmed cell death and sensitized skin cancer cells to conventional anti-cancer drugs via ROS-mediated JNK activation.</p><h2>Other Information</h2><p dir="ltr">Published in: Biomedicine & Pharmacotherapy<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.biopha.2022.113950" target="_blank">https://dx.doi.org/10.1016/j.biopha.2022.113950</a></p>2022-12-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.biopha.2022.113950https://figshare.com/articles/journal_contribution/Pristimerin_mediated_anticancer_effects_and_sensitization_of_human_skin_cancer_cells_through_modulation_of_MAPK_signaling_pathways/24516421CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/245164212022-12-01T00:00:00Z
spellingShingle Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathways
Maha Al-Tamimi (17280550)
Biomedical and clinical sciences
Clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Pristimerin
Squamous cell carcinoma
Signal transduction
Autophagy
Apoptosis
JNK
status_str publishedVersion
title Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathways
title_full Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathways
title_fullStr Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathways
title_full_unstemmed Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathways
title_short Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathways
title_sort Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathways
topic Biomedical and clinical sciences
Clinical sciences
Oncology and carcinogenesis
Pharmacology and pharmaceutical sciences
Pristimerin
Squamous cell carcinoma
Signal transduction
Autophagy
Apoptosis
JNK