Molecular mechanisms of ROS-modulated cancer chemoresistance and therapeutic strategies

Zhou, Xiaoting; An, Biao; Lin, Yong; Ni, Yanghong; Zhao, Xiulan; Liang, Xiao

doi:10.1016/j.biopha.2023.115036

Cited by 23 publications

(13 citation statements)

References 217 publications

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“…Following PRDX2 knockdown, our analysis revealed an increased accumulation of ROS in tumors 8 . Platinum‐based drugs exert their antitumor effects by inducing DNA damage via ROS 27 . However, PRDX2 overexpression increases ROS clearance, diminishing cisplatin's tumor‐killing efficacy.…”

Section: Discussionmentioning

confidence: 89%

PRDX2 regulates stemness contributing to cisplatin resistance and metastasis in bladder cancer

Li,

Wang,

Zhu

et al. 2024

Environmental Toxicology

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BackgroundCisplatin (CDDP)‐based chemotherapy has emerged as the primary treatment for muscle‐invasive bladder cancer and metastatic bladder cancer. Nevertheless, a significant proportion of patients experience rapidly developed chemoresistance, leading to treatment ineffectiveness. Existing evidence suggests that chemoresistance is governed by various factors, including tumor stem cells, epithelial mesenchymal transition, and reactive oxygen species (ROS). However, limited research has been conducted on the role of PRDX2, a crucial ROS scavenger, in the modulation of chemoresistance in bladder cancer.MethodsCisplatin‐resistant cell lines were established using the concentration gradient overlay method, and differentially expressed genes in resistant cells were screened through RNA sequencing. The expression of PRDX2 in cells and tissues was assessed using RT‐qPCR, Western Blot, and immunohistochemistry. The expression of PRDX2 in bladder cancer and adjacent tissues was evaluated using a bladder cancer tissue microarray. Furthermore, the impact of PRDX2 knockdown on tumor formation and metastasis was investigated in vivo by applying subcutaneous tumor xenografts tail vein metastasis assays.ResultsWe demonstrated that PRDX2 is significantly upregulated in bladder tumors and cisplatin‐resistant bladder tumor cell lines. Overexpression of PRDX2 can promote tumor proliferation, migration, and invasion both in vitro and in vivo. We have found that knockdown of PRDX2 expression can effectively reverse cell resistance to cisplatin. Mechanistically, our findings suggest that PRDX2 is involved in regulating tumor stemness and epithelial‐mesenchymal transition (EMT). Knockdown of PRDX2 affects the PI3K‐AKT and mTOR signaling pathways, thereby influencing tumor stemness and EMT, ultimately impacting the chemotherapy resistance of the tumor.ConclusionsThis study provides a new insight into the regulation of chemotherapy resistance in bladder cancer by PRDX2. Targeting PRDX2 can serve as a potent therapeutic target for chemotherapy resistance.

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Section: Discussionmentioning

confidence: 89%

PRDX2 regulates stemness contributing to cisplatin resistance and metastasis in bladder cancer

Li,

Wang,

Zhu

et al. 2024

Environmental Toxicology

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“…165,166 The leading characteristic of ROS is the high reactivity, which has led to the existence of diverse ROSmediated reactions within biological environments. 167 ROS have abundant intracellular sources including NADPH oxidase, 168 xanthine oxidases, cyclooxygenases, 169 and mitochondria 170 among others. Apart from endogenous ROS sources, many exogenous sources such as agent ionization and radiation can further stimulate ROS generation.…”

Section: Ros-responsive Cpt Prodrug Nanomedicinesmentioning

confidence: 99%

Camptothecin-based prodrug nanomedicines for cancer therapy

Zhang,

Yu,

Guo

et al. 2023

Nanoscale

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“…Increased GSH significantly reduces oxidative damage and leads drug resistance in cancer cells 20 . Moreover, GSH depletion causes more reactive oxygen species (ROS) production that activates the transcription of apoptosis‐associated genes 21 . Therefore, alteration of GSH and intracellular ROS can be an alternate potential strategy to reverse MDR in cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

“…ROS plays a crucial role in the growth, progression, and stemness of cancer cells 22 . Optimum ROS generation exerts tumor‐promoting effects by interacting with several proteins and intracellular signal transduction pathways contributing to tumor proliferation and survival 21 . However, at higher levels, ROS tends to damage proteins, nucleic acid, cell membranes, and organelles causing cell death 23 .…”

Section: Introductionmentioning

confidence: 99%

“…22 Optimum ROS generation exerts tumor-promoting effects by interacting with several proteins and intracellular signal transduction pathways contributing to tumor proliferation and survival. 21 However, at higher levels, ROS tends to damage proteins, nucleic acid, cell membranes, and organelles causing cell death. 23 Several chemotherapeutic drugs disrupt redox homeostasis in cancer cells by producing intracellular ROS.…”

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confidence: 99%

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Andrographolide reverts multidrug resistance in KBCh^R 8‐5 cells through AKT signaling pathway

Lakra,

Bharathiraja,

Dhanalakshmi

et al. 2024

Cell Biochemistry & Function

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Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy. P‐glycoprotein (P‐gp) one of the ATP‐binding cassette (ABC) transporters plays an important role in MDR. In this study, we examined the sensitizing property of andrographolide (Andro) to reverse MDR in the drug‐resistant KBChR 8‐5 cells. Andro exhibited increased cytotoxicity in a concentration‐dependent manner in the P‐gp overexpressing KBChR 8‐5 cells. Furthermore, Andro showed synergistic interactions with PTX and DOX in this drug‐resistant cells. Andro co‐administration enhanced PTX‐ and DOX‐induced cytotoxicity and reduced cell proliferation in the MDR cancer cells. Moreover, reactive oxygen species (ROS) were elevated with a decrease in the mitochondrial membrane potential (MMP) during Andro and chemotherapeutic drugs combination treatment in the drug‐resistant cells. Furthermore, Andro and PTX‐induced cell cycle arrest was observed in the drug‐resistant cell. We also noticed that the expression of ABCB1 and AKT were downregulated during Andro (4 µM) treatment. Furthermore, Andro treatment enhanced the expression of caspase 3 and caspase 9 in the combinational groups that support the enhanced apoptotic cell death in drug‐resistant cancer cells. Therefore, the results reveal that Andro plays a role in the reversal of P‐gp‐mediated MDR in KBChR 8‐5 cells which might be due to regulating ABCB1/AKT signaling pathway.

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Molecular mechanisms of ROS-modulated cancer chemoresistance and therapeutic strategies

Cited by 23 publications

References 217 publications

PRDX2 regulates stemness contributing to cisplatin resistance and metastasis in bladder cancer

PRDX2 regulates stemness contributing to cisplatin resistance and metastasis in bladder cancer

Camptothecin-based prodrug nanomedicines for cancer therapy

Andrographolide reverts multidrug resistance in KBCh^R 8‐5 cells through AKT signaling pathway

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Molecular mechanisms of ROS-modulated cancer chemoresistance and therapeutic strategies

Cited by 23 publications

References 217 publications

PRDX2 regulates stemness contributing to cisplatin resistance and metastasis in bladder cancer

PRDX2 regulates stemness contributing to cisplatin resistance and metastasis in bladder cancer

Camptothecin-based prodrug nanomedicines for cancer therapy

Andrographolide reverts multidrug resistance in KBChR 8‐5 cells through AKT signaling pathway

Contact Info

Product

Resources

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Andrographolide reverts multidrug resistance in KBCh^R 8‐5 cells through AKT signaling pathway