L-lysine Increases the Anticancer Effect of Doxorubicin in Breast Cancer by Inducing ROS-Dependent Autophagy

Title:L-lysine Increases the Anticancer Effect of Doxorubicin in Breast Cancer by Inducing ROS-Dependent Autophagy

Volume: 24

Author(s): Mozhgan Jahani, Reza Yarani, Davood Rezazadeh, Hadis Tahmasebi, Zohreh Hoseinkhani, Sara Kiani and Kamran Mansouri*

Affiliation:

• Department of Molecular Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
• Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract: Background: Doxorubicin (DOX) is a chemotherapy drug that is widely used in cancer therapy, especially in Triple-Negative Breast Cancer (TNBC) patients. Nevertheless, cytoprotective autophagy induction by DOX limits its cytotoxic effect and drug resistance induction in patients. Therefore, finding a new way is essential for increasing the effectiveness of this drug for cancer treatment.

Objective: This study aimed to investigate the effect of L-lysine on DOX cytotoxicity, probably through autophagy modulation in TNBC cell lines.

Methods: We used two TNBC cell lines, MDA-MB-231 and MDA-MB-468, with various levels of autophagy activity. Cell viability after treatment with L-lysine alone and in combination therapy was evaluated by MTT assay. Reactive Oxygen Species (ROS), nitric oxide (NO) concentration, and arginase activity were assessed using flow cytometric analysis, Griess reaction, and arginase activity assay kit, respectively. Real-time PCR and western blot analysis were used to evaluate the L-lysine effect on the autophagy-related genes and protein expression. Cell cycle profile and apoptotic assay were performed using flow cytometric analysis.

Results: The obtained data indicated that L-lysine in both concentrations of 24 and 32 mM increased the autophagy flux and enhanced the DOX cytotoxicity, especially in MDA-MB-231, which demonstrated higher autophagy activity than MDA-MB-468, by inducing ROS and NO production. Furthermore, L-lysine induced G2/M arrest autophagy cell death, while significant apoptotic changes were not observed.

Conclusion: These findings suggest that L-lysine can increase DOX cytotoxicity through autophagy modulation. Thus, L-lysine, in combination with DOX, may facilitate the development of novel adjunct therapy for cancer.

Cite this article as:

Jahani Mozhgan, Yarani Reza, Rezazadeh Davood, Tahmasebi Hadis, Hoseinkhani Zohreh, Kiani Sara and Mansouri Kamran*, L-lysine Increases the Anticancer Effect of Doxorubicin in Breast Cancer by Inducing ROS-Dependent Autophagy, Current Cancer Drug Targets 2024; 24 () . https://dx.doi.org/10.2174/0115680096288665240315072646