Linoleic Acid–Glucosamine Hybrid for Endogenous Iron-Activated Ferroptosis Therapy in High-Grade Serous Ovarian Cancer

Chen, Ying; Liao, Xiaoming; Pei, Jing; Hu, Liangkui; Yang, Zengqiu; Yao, Yongchao; Liao, Chunyan; Zhang, Shiyong

doi:10.1021/acs.molpharmaceut.2c00333

Cited by 9 publications

(3 citation statements)

References 77 publications

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“…Chen et al. ( 100 ) developed a hybrid compound called linoleic acid (LA)-glucosamine (GlcN) (LA-GlcN) as an effective treatment for high-grade serous ovarian cancer (HGSOC). The unique feature of this compound is that GlcN specifically targets and recognizes the overexpressed glucose transporter 1 (GLUT 1) in tumor cells, thereby enhancing the uptake of LA-GlcN.…”

Section: Treatment Based On Ferroptosismentioning

confidence: 99%

The mechanisms crosstalk and therapeutic opportunities between ferroptosis and ovary diseases

Yu¹,

Wang²,

Jiang³

et al. 2023

Front. Endocrinol.

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Ferroptosis, a form of regulated cell death, was first defined in 2012. Ferroptosis mainly involves iron-driven lipid peroxidation damage of cells. This process is regulated by iron homeostasis, redox balance, lipid metabolism, glutathione metabolism, and various disease signaling pathways. Iron is one of the key mineral elements that regulate the physiological function of women and the development of ovarian tumors. Occurrence of Ferroptosis has some hidden dangers and advantages in ovary diseases. Some scholars have shown that ferroptosis of ovarian granulosa cells (GC) promotes the development of ovarian dysfunction and polycystic ovary syndrome (PCOS). Interestingly, drug-resistant ovarian cancer cells are very sensitive to ferroptosis, suggesting that pharmacological positive and negative regulation of ferroptosis has great potential in the treatment of benign ovarian diseases and ovarian cancer. This article aimed to assess how ferroptosis occurs and the factors controlling ferroptosis. Moreover, we summarize how ferroptosis can be used to predict, diagnose and target treatment ovary disease. Meanwhile, we also evaluated the different phenomena of Ferroptosis in ovarian diseases. It aims to provide new directions for the research and prevention of female reproductive diseases.

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Section: Treatment Based On Ferroptosismentioning

confidence: 99%

The mechanisms crosstalk and therapeutic opportunities between ferroptosis and ovary diseases

Yu¹,

Wang²,

Jiang³

et al. 2023

Front. Endocrinol.

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“…[8] Moreover, lysosomes are highly acidic (≈pH 4.5-5.0) [15] and rich in loosely bound iron ions (II). [16] Therefore, VC@ N3AM cLAVs in lysosomes were more likely to accelerate the conversion of H 2 O 2 into highly reactive hydroxyl radicals (•OH), thereby causing more significant cytotoxicity. The efficacy of VC@ N3AM cLAVs was further validated in triple-negative breast cancer 4T1 cells.…”

Section: In Vitro Anticancer Effect Evaluation Of Vc@ N3am Clavsmentioning

confidence: 99%

Boosting ROS‐Mediated Lysosomal Membrane Permeabilization for Cancer Ferroptosis Therapy

Chen

Yang

Wang

et al. 2022

Adv Healthcare Materials

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Due to the deficient catalase, abundant reduced iron and low acidic environment in lysosomes, inducing lysosomal membrane permeabilization (LMP) through Fenton reaction-based reactive oxygen species (ROS) generation recently attracts increasing attention in cancer therapy. However, the lysosomal membranes are protected by highly glycosylated membrane proteins and several endolysosomal damage-response mechanisms can rapidly repair the injured lysosomes. To produce sufficient ROS and cause complete lysosomal membranes rupture, a lysosome-targeted ROS inducer, N-(3-Aminopropyl) morpholine grafted cross-linked lipoic acid vesicles with vitamin C-loading (VC@ N3AM cLAVs), is developed. VC@ N3AM cLAVs efficiently accumulate in lysosomes and convert into two redox couples LA/DHLA (dihydrolipoic acid, reduced form of LA) and VC/DHA (dehydroascorbic acid, oxidized form of VC) by the lysosomal glutathione, which can not only produce a large amount of H 2 O 2 by pro-oxidant action but also accelerate iron transformation through the cyclic redox reactions between each other and cause the efficient conversion of the generated H 2 O 2 into highly toxic •OH. Both in vitro and in vivo experiments demonstrate that VC@ N3AM cLAVs can effectively enhance ROS production and boost LMP, finally initiation irreversible death of tumor cells via ferroptosis pathway, thus representing a potential anticancer drug for cancer therapy.

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“…Although surgery, chemotherapy, angiogenesis inhibitors, poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors and immunotherapy provide more options for ovarian cancer treatment, but in most cases, it is still difficult for patients to obtain satisfactory treatment results [ 3 , 4 ]. Therefore, finding a newer, reliable and potent new drug is more meaningful for the treatment and prognosis of ovarian cancer [ 5 , 6 ]. Ferroptosis, proposed by Dixon et al in 2012, is a non-apoptotic form of cell death that is highly dependent on intracellular iron ions and lipid peroxides accumulation as its main feature, and can selectively kill cancer cells such as ovarian tumor cells [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Portulaca oleracea L. polysaccharide inhibits ovarian cancer via inducing ACSL4-dependent ferroptosis

Xia,

Yang,

Liu

2024

Aging

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The antitumor effect of Portulaca oleracea L. polysaccharide (POL) has been demonstrated, but whether it curbs the development of ovarian cancer has not been reported. Here, we treated ovarian cancer cells with different concentrations of POL, detected cell activity by CCK-8 assay, and apoptosis rate by flow cytometry. The results showed that SKOV3 and Hey cell survival decreased with increasing POL concentration in a dose-dependent manner. POL significantly inhibited ovarian cancer cell migration and increased cell death compared with the control group. Ferroptosis inhibitors, but not apoptosis, necrosis, and autophagy inhibitors, reversed POL-induced cell death. Further studies revealed that POL promoted the accumulation of lipid reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), and decreased glutathione (GSH) production. Moreover, POL significantly increased the mortality of ovarian cancer cells. In vivo studies confirmed that POL reduced the volume and weight of tumors and increased the levels of Fe2+ and MDA in mice in vivo . Western blot assay revealed that POL increased the expression of ACSL4 in ovarian cancer cells as well as in tumors in mice in vivo . More importantly, the POL-mediated increase in lipid ROS, Fe2+, MDA, and decrease in GSH were significantly reversed after knocking down ACSL4 in ovarian cancer cells. Thus, POL can effectively inhibit ovarian cancer development, which may be achieved by increasing ACSL4-mediated ferroptosis. These results suggest that POL has the potential to be a potential drug for targeted treatment of ovarian cancer.

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Linoleic Acid–Glucosamine Hybrid for Endogenous Iron-Activated Ferroptosis Therapy in High-Grade Serous Ovarian Cancer

Cited by 9 publications

References 77 publications

The mechanisms crosstalk and therapeutic opportunities between ferroptosis and ovary diseases

The mechanisms crosstalk and therapeutic opportunities between ferroptosis and ovary diseases

Boosting ROS‐Mediated Lysosomal Membrane Permeabilization for Cancer Ferroptosis Therapy

Portulaca oleracea L. polysaccharide inhibits ovarian cancer via inducing ACSL4-dependent ferroptosis

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