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

journal contribution
submitted on 2023-11-08, 09:47 and posted on 2023-11-08, 11:08 authored by Maha Al-Tamimi, Abdul Q. Khan, Rasheeda Anver, Fareed Ahmad, Jericha M Mateo, Syed Shadab Raza, Majid Alam, Joerg Buddenkotte, Martin Steinhoff, Shahab Uddin

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.

Other Information

Published in: Biomedicine & Pharmacotherapy
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Open Access funding provided by the Qatar National Library



  • English



Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License

Institution affiliated with

  • Hamad Medical Corporation
  • Academic Health System - HMC
  • Dermatology Institute - HMC
  • Interim Translational Research Institute - HMC
  • Rumailah Hospital - HMC
  • Qatar University
  • Laboratory Animal Research Center - QU
  • Qatar University Health - QU
  • College of Medicine - QU HEALTH
  • Weill Cornell Medicine - Qatar