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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1412565

Rhus coriaria induces autophagic and apoptotic cell death in pancreatic cancer cells

Provisionally accepted
Yassine El Mahi Yassine El Mahi 1Zohra N. Nizami Zohra N. Nizami 1Adil Wali Adil Wali 2Aysha Al Neyadi Aysha Al Neyadi 3Mohamed Magramane Mohamed Magramane 1Mazoun Al Azzani Mazoun Al Azzani 1Kholoud F. Arafat Kholoud F. Arafat 1Samir Attoub Samir Attoub 1Ali H. Eid Ali H. Eid 4Rabah Iratni Rabah Iratni 1*
  • 1 United Arab Emirates University, Al-Ain, United Arab Emirates
  • 2 RAK Medical and Health Sciences University, Ras al-Khaimah, Ras al-Khaimah, United Arab Emirates
  • 3 Fatima College of Health​ Sciences, Abu Dhabi, United Arab Emirates
  • 4 Qatar University, Doha, Qatar

The final, formatted version of the article will be published soon.

    Pancreatic cancer is a leading cause of cancer-related mortality worldwide with increasing global incidence. We previously reported the anticancer effect of Rhus coriaria ethanolic extract (RCE) in triple negative breast and colon cancer cells. Herein, we investigated the anticancer effect of RCE on human pancreatic cancer cells. We found that RCE significantly inhibited the viability and colony growth of pancreatic cancer cells (Panc-1, Mia-PaCa-2, S2-013, AsPC-1). The antiproliferative effects of RCE in pancreatic cancer cells (Panc-1 and Mia-PaCa-2) were mediated through induction of G1 cell cycle arrest, Beclin-1-independent autophagy, and apoptosis. RCE activated both the extrinsic and intrinsic pathways of apoptosis and regulated the Bax/Bcl-2 apoptotic switch. Mechanistically, we found that RCE inhibited the AKT/mTOR pathway, downstream of which, inactivation of the cell cycle regulator p70S6K and downregulation of the antiapoptotic protein survivin was observed. Additionally, we found that RCE-induced autophagy preceded apoptosis. Further, we confirmed the anticancer effect of RCE in a chick embryo xenograft model and found that RCE inhibited the growth of pancreatic cancer xenografts without affecting embryo survival. Collectively, our findings demonstrate that Rhus coriaria exerts potent anti-pancreatic cancer activity though cell cycle impairment, autophagy, and apoptosis, and is hence a promising source of anticancer phytochemicals.

    Keywords: Rhus coriaria, Pancreatic Cancer, Autophagy, Apoptosis, Akt/mTOR pathway

    Received: 05 Apr 2024; Accepted: 10 Jul 2024.

    Copyright: © 2024 El Mahi, Nizami, Wali, Al Neyadi, Magramane, Al Azzani, Arafat, Attoub, Eid and Iratni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Rabah Iratni, United Arab Emirates University, Al-Ain, United Arab Emirates

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