Rhein Induces Oral Cancer Cell Apoptosis and ROS via Suppresse AKT/mTOR Signaling Pathway In Vitro and In Vivo

Sep 24, 2026

Oral cancer remains a leading global cause of death, and the role of rhein in this disease is not fully clarified. Rhein, a natural compound derived from traditional Chinese herbal medicine rhubarb, is evaluated for anticancer potential against oral cancer cells and xenografts. Cell growth, migration, invasion, cell cycle, apoptosis, and ROS levels are analyzed, alongside AKT/mTOR pathway activity and epithelial–mesenchymal transition-related proteins. Results support apoptosis and ROS accumulation with AKT/mTOR pathway suppression as key mechanisms.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Keywords

1. Introduction

Autophagy and mTOR signaling

ROS and cancer regulation

Rhein as a phytochemical

Article Rhein Induces Oral Cancer Cell Apoptosis and ROS via Suppresse AKT/mTOR Signaling Pathway In Vitro and In Vivo Haibo Zhang 1,2,3,†, Lei Ma 1,2,†, Eungyung Kim 1,2, Junkoo Yi 4, Hai Huang 1,2, Hyeonjin Kim 1,2, Muhammad Atif Raza 1,2, Sijun Park 5, Soyoung Jang 5, Kirim Kim 6, Sung-Hyun Kim 7, Youngkyun Lee 8, Eunkyong Kim 6, Zae Young Ryoo 5 and Myoung Ok Kim 1,2, * Citation: Zhang, H.; Ma, L.; Kim, E.; Yi, J.; Huang, H.; Kim, H.; Raza, M.A.; Park, S.; Jang, S.; Kim, K.; et al. Rhein Induces Oral Cancer Cell Apoptosis and ROS via Suppresse AKT/mTOR Signaling Pathway In Vitro and In Vivo. Int. J. Mol. Sci. 2023, 24, 8507 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms24108507 Academic Editor: Faisal Aziz Received: 3 April 2023 Revised: 24 April 2023 Accepted: 6 May 2023 Published: 9 May 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Animal Science and Biotechnology, Kyungpook National University, Sangju 37224, Republic of Korea 2 Department of Animal Biotechnology, Research Center for Horse Industry, Kyungpook National University, Sangju 37224, Republic of Korea 3 College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China 4 School of Animal Life Convergence Science, Hankyung National University, Anseong 17579, Republic of Korea 5 School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea 6 Department of Dental Hygiene, Kyungpook National University, Sangju 37224, Republic of Korea 7 Department of Bio-Medical Analysis, Korea Polytechnic College, Chungnam 34134, Republic of Korea 8 School of Dentistry, Kyungpook National University, Daegu 41566, Republic of Korea * Correspondence: [ok4325@knu.ac.kr](ok4325@knu.ac.kr); Tel.: +82-54-530-1234 † These authors contributed equally to this work. Abstract: Oral cancer remains the leading cause of death worldwide. Rhein is a natural compound extracted from the traditional Chinese herbal medicine rhubarb, which has demonstrated therapeutic effects in various cancers. However, the speciﬁc effects of rhein on oral cancer are still unclear. This study aimed to investigate the potential anticancer activity and underlying mechanisms of rhein in oral cancer cells. The antigrowth effect of rhein in oral cancer cells was estimated by cell proliferation, soft agar colony formation, migration, and invasion assay. The cell cycle and apoptosis were detected by ﬂow cytometry. The underlying mechanism of rhein in oral cancer cells was explored by immunoblotting. The in vivo anticancer effect was evaluated by oral cancer xenografts. Rhein signiﬁcantly inhibited oral cancer cell growth by inducing apoptosis and S-phase cell cycle arrest. Rhein inhibited oral cancer cell migration and invasion through the regulation of epithelial– mesenchymal transition-related proteins. Rhein induced reactive oxygen species (ROS) accumulation in oral cancer cells to inhibit the AKT/mTOR signaling pathway. Rhein exerted anticancer activity in vitro and in vivo by inducing oral cancer cell apoptosis and ROS via the AKT/mTOR signaling pathway in oral cancer. Rhein is a potential therapeutic drug for oral cancer treatment. Keywords: apoptosis; autophagy; mTOR; oral cancer; rhein 1. Introduction Oral cancer (OC) is a type of head and neck cancer and is one of the most common malignancies worldwide [1] . Approximately 90% of oral and oropharyngeal malignancies aresquamous cell carcinomas [2] . Despite new diagnostic techniques and treatment strategies for OC treatment, the disease remains a critical challenge because

FAQs

What was the study’s main goal regarding rhein and oral cancer?

To evaluate the anticancer activity of rhein in oral cancer cells and to clarify the underlying mechanisms involved.

How did the researchers assess rhein’s effects on oral cancer cells?

They measured antigrowth activity using proliferation and colony formation assays, and migration and invasion assays; they assessed cell cycle and apoptosis by flow cytometry and used immunoblotting to explore mechanisms.

What signaling mechanism does the study link to rhein’s anticancer effects?

The study reports that rhein induces ROS accumulation and suppresses the AKT/mTOR signaling pathway, leading to apoptosis and S-phase cell cycle arrest, while regulating epithelial–mesenchymal transition-related proteins.

Sep 24, 2026

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