Multidrug resistance reversal effect of tenacissoside I through impeding EGFR methylation mediated by PRMT1 inhibition.
10.1016/S1875-5364(25)60956-3
- Author:
Donghui LIU
1
;
Qian WANG
1
;
Ruixue ZHANG
1
;
Ruixin SU
1
;
Jiaxin ZHANG
1
;
Shanshan LIU
1
;
Huiying LI
1
;
Zhesheng CHEN
2
;
Yan ZHANG
3
;
Dexin KONG
4
;
Yuling QIU
5
Author Information
1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
2. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
3. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: zhangyan_929@yeah.net.
4. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. Electronic address: kongdexin@tmu.edu.cn.
5. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. Electronic address: qiuyuling@tmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
EGFR signaling;
Multidrug resistance reversal effect;
PRMT1;
Protein methylation;
Tenacissoside I
- MeSH:
Humans;
Protein-Arginine N-Methyltransferases/antagonists & inhibitors*;
Drug Resistance, Neoplasm/drug effects*;
ErbB Receptors/genetics*;
Animals;
Cell Line, Tumor;
Drug Resistance, Multiple/drug effects*;
Methylation/drug effects*;
Saponins/administration & dosage*;
Mice;
Mice, Nude;
Mice, Inbred BALB C;
ATP Binding Cassette Transporter, Subfamily B/genetics*;
Doxorubicin/pharmacology*;
Paclitaxel/pharmacology*;
Female;
Repressor Proteins
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(9):1092-1103
- CountryChina
- Language:English
-
Abstract:
Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
