Dihydroartemisinin Triggers Ferroptosis in Multidrug-Resistant Leukemia Cells

Zhang, Xueyan; Ai, Ziying; Zhang, Zhewen; Dong, Rui; Wang, Lina; Jin, Suya; Wei, Hulai

doi:10.1089/dna.2021.1145

Cited by 16 publications

(9 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, this study also revealed Andro‐mediated decrease in GSH activity within PTX and DOX‐treated resistant KBCh R 8‐5 cancer cells. In a similar study, dihydroartemisinin (DHA), a metabolite derived from artemisinin herbal compound, decreased GSH levels in multidrug‐resistant leukemia cells 55 . Apigenin‐mediated decrease in GSH levels was observed in ABCC1 expressing tumor cells 56 .…”

Section: Discussionmentioning

confidence: 88%

“…In a similar study, dihydroartemisinin (DHA), a metabolite derived from artemisinin herbal compound, decreased GSH levels in multidrug-resistant leukemia cells. 55 Apigenin-mediated decrease in GSH levels was observed in ABCC1 expressing tumor cells. 56 The disruption of cell integrity serves as an indicator of the cell death process, as demonstrated in this study.…”

Section: Effect Of Andro On Expression Of Abcb1 and Akt In Kbch R 8-5...mentioning

confidence: 97%

See 1 more Smart Citation

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

Lakra,

Bharathiraja,

Dhanalakshmi

et al. 2024

Cell Biochemistry & Function

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 88%

Section: Effect Of Andro On Expression Of Abcb1 and Akt In Kbch R 8-5...mentioning

confidence: 97%

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

Lakra,

Bharathiraja,

Dhanalakshmi

et al. 2024

Cell Biochemistry & Function

View full text Add to dashboard Cite

show abstract

“…In the multidrug-resistant K562/adriamycin (ADM) leukemia cell line, dihydroartemisinin reversed ferroptosis resistance by modulation of the expression levels of GPX4 and proteins involved in iron homeostasis and contributed to cell resensitization toward ADM (Zhang et al, 2022d ). Artemisinin derivatives also displayed interesting antiproliferative properties in lung cancer cells (Zhang et al, 2021c ).…”

Section: Natural Compounds As Ferroptosis Inducersmentioning

confidence: 99%

Novel Insights on Ferroptosis Modulation as Potential Strategy for Cancer Treatment: When Nature Kills

Consoli

Fallica

Sorrenti

et al. 2024

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Significance: The multifactorial nature of the mechanisms implicated in cancer development still represents a major issue for the success of established antitumor therapies. The discovery of ferroptosis, a novel form of programmed cell death distinct from apoptosis, along with the identification of the molecular pathways activated during its execution, has led to the uncovering of novel molecules characterized by ferroptosis-inducing properties. Recent advances: As of today, the ferroptosis-inducing properties of compounds derived from natural sources have been investigated and interesting findings have been reported both in vitro and in vivo . Critical Issues: Despite the efforts made so far, only a limited number of synthetic compounds have been identified as ferroptosis inducers, and their utilization is still limited to basic research. In this review, we analyzed the most important biochemical pathways involved in ferroptosis execution, with particular attention to the newest literature findings on canonical and non-canonical hallmarks, together with mechanisms of action of natural compounds identified as novel ferroptosis inducers. Compounds have been classified based on their chemical structure, and modulation of ferroptosis-related biochemical pathways has been reported. Future Directions: The outcomes herein collected represent a fascinating starting point from which to take hints for future drug discovery studies aimed at identifying ferroptosis-inducing natural compounds for anticancer therapies. Antioxid. Redox Signal. 40, 40–85.

show abstract

“…Signaling pathways, such as AKT/mTOR, may be modulated by DHA, influencing cellular responses to oxidative stress. The potential of DHA to induce ferroptosis highlights its relevance as a novel therapeutic strategy, particularly in combatting drug-resistant cancers ( Zhang X. et al, 2022 ). Notably, Fe3O4-PGA nanoparticles can be utilized to encapsulate DHA through a solvothermal synthesis approach.…”

Section: Targeting Pi3k/akt To Induce Ferroptosismentioning

confidence: 99%

Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer

Su,

Peng,

Liu

2024

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The global challenge posed by cancer, marked by rising incidence and mortality rates, underscores the urgency for innovative therapeutic approaches. The PI3K/Akt signaling pathway, frequently amplified in various cancers, is central in regulating essential cellular processes. Its dysregulation, often stemming from genetic mutations, significantly contributes to cancer initiation, progression, and resistance to therapy. Concurrently, ferroptosis, a recently discovered form of regulated cell death characterized by iron-dependent processes and lipid reactive oxygen species buildup, holds implications for diseases, including cancer. Exploring the interplay between the dysregulated PI3K/Akt pathway and ferroptosis unveils potential insights into the molecular mechanisms driving or inhibiting ferroptotic processes in cancer cells. Evidence suggests that inhibiting the PI3K/Akt pathway may sensitize cancer cells to ferroptosis induction, offering a promising strategy to overcome drug resistance. This review aims to provide a comprehensive exploration of this interplay, shedding light on the potential for disrupting the PI3K/Akt pathway to enhance ferroptosis as an alternative route for inducing cell death and improving cancer treatment outcomes.

show abstract

Dihydroartemisinin Triggers Ferroptosis in Multidrug-Resistant Leukemia Cells

Cited by 16 publications

References 32 publications

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

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

Novel Insights on Ferroptosis Modulation as Potential Strategy for Cancer Treatment: When Nature Kills

Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer

Contact Info

Product

Resources

About

Dihydroartemisinin Triggers Ferroptosis in Multidrug-Resistant Leukemia Cells

Cited by 16 publications

References 32 publications

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

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

Novel Insights on Ferroptosis Modulation as Potential Strategy for Cancer Treatment: When Nature Kills

Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer

Contact Info

Product

Resources

About

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

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