Danshen Improves Survival of Patients With Breast Cancer and Dihydroisotanshinone I Induces Ferroptosis and Apoptosis of Breast Cancer Cells

Lin, Yang-Hua; Shen, Yi-Chia; Wu, Ching‐Yuan; Tsai, Ying-Ying; Yang, Ya‐Chen; Lin, Yin-Yin; Kuan, Feng‐Che; Lu, Cheng-Nan; Chang, Geng‐He; Tsai, Ming‐Shao; Hsu, Cheng‐Ming; Yeh, Reming-Albert; Yang, Pei-Rung; Lee, I-Yun; Shu, Li-Hsin; Cheng, Yu‐Ching; Liu, Hung-Te; Wu, Yu-Huei; Wu, Yu-Heng; Chang, Deching

doi:10.3389/fphar.2019.01226

Cited by 86 publications

(51 citation statements)

References 40 publications

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“…A previous study indicated that tanshen induced ferroptosis in breast cancer cells, and significantly reduced the final tumor volume in a xenograft nude mouse model without adverse effects (31). Therefore, the present study aimed to evaluate the effects of DHI on the proliferation of glioma cells and investigate the contribution of ferroptosis to the underlying mechanism.…”

Section: Introductionmentioning

confidence: 93%

Dihydrotanshinone I inhibits human glioma cell proliferation via the activation of ferroptosis

2020

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The aim of the present study was to investigate the effect of dihydrotanshinone I (DHI) on the survival of human glioma cells and the expression levels of ferroptosis-associated proteins. Human U251 and U87 glioma cells were cultured in vitro and treated with different concentrations of DHI and/or the ferroptosis inhibitor ferrostatin-1. A Cell Counting Kit-8 assay was used to determine the cell survival rate. The cells were further analyzed to determine their 5-, 12-and 15-hydroxyeicosatetraenoic acid (HETE), lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios. Western blotting was used to detect ferroptosis-associated glutathione peroxidase 4 (GPX4) and long-chain acyl-CoA synthetase 4 (ACSL-4). Changes in the mitochondrial membrane potential (MMP) were also observed using tetramethylrhodamine methyl ester staining and confocal fluorescence microscopy. The results revealed that DHI inhibited the proliferation of human glioma cells. Following treatment of the U251 and U87 cells with DHI, changes in the expression levels of ferroptosis-associated proteins were observed; the expression level of GPX4 decreased and that of ACSL-4 increased. DHI also increased the levels of LDH and MDA in the human glioma cells and reduced the GSH/GSSG ratio. The DHI-treated cells also exhibited a marked reduction in MMP. Furthermore, ferrostatin-1 blocked the DHI-induced effects in human glioma cells. From these results, it may be concluded that DHI inhibits the proliferation of human glioma cells via the induction of ferroptosis.

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Section: Introductionmentioning

confidence: 93%

Dihydrotanshinone I inhibits human glioma cell proliferation via the activation of ferroptosis

2020

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“…Long non-coding RNAs (LncRNAs) have important roles in ferroptosis. For instance, lncRNA GABPB1-AS1 can down-regulate the GABPB1 level and inhibit its Zhang, K et al [84] Inhibit the expression of TFR1 Reduce the accumulation of Glu Decrease the depletion of Glu antioxidant capacity, thereby inducing ferroptosis in hepatic cancer cells [77].…”

Section: Ferroptosis and Hepatocellular Cancermentioning

confidence: 99%

“…Another study reported that the down-regulation of lncRNA P53RRA promoted ferroptosis by sequestering p53 in the nucleus [83]. In addition, as a herb widely used in traditional Chinese medicine, danshen has been reported to improve the prognosis of breast cancer, which may be due to the effects of its bioactive compound, dihydroisotanshinone I, in repressing the protein GPX4 expression and inducing ferroptosis [84].…”

Section: Ferroptosis and Breast Cancermentioning

confidence: 99%

Novel insights on targeting ferroptosis in cancer therapy

Zuo

Pan

et al. 2020

Biomark Res

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Ferroptosis belongs to a novel form of regulated cell death. It is characterized by iron dependence, destruction of intracellular redox balance and non-apoptosis. And cellular structure and molecules level changes also occur abnormally during ferroptosis. It has been proved that ferroptosis exist widespreadly in many diseases, such as heart disease, brain damage or alzheimer disease. At the same time, the role of ferroptosis in cancer cannot be underestimated. More and more indications have told that ferroptosis is becoming a powerful weapon against cancer. In addition, therapies rely on ferroptosis have been applied to the clinic. Therefore, it is necessary to understand this newly discovered form of cell death and its connection with cancer. This review summarizes the mechanism of ferroptosis, ferroptosis inducers based on different targets and inspection methods. At last, we analyzed the relationship between ferroptosis and malignancies, in order to provide a novel theory basis for cancer treatment.

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“…demonstrated that Danshen, a traditional Chinese medicine, prolonged survival of patients with breast cancer by inducing cell ferroptosis [25]. Similarly, a study published in 2018 reported that natural compounds exerted antitumor activity through the induction of non-apoptotic programmed cell death, including ferroptosis [26], which provided an effective therapeutic strategy for patients with cancer.…”

Section: Introductionmentioning

confidence: 97%

Curcumin Suppresses Tumorigenesis via Promoting SLC1A5-mediated Ferroptosis in Breast Cancer

Cao¹,

Li²,

Wang³

et al. 2020

Preprint

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Background: Breast cancer is one of the most malignant tumors in the female. Previous studies confirmed that Curcumin, a kind of polyphenol compound extract from the Curcuma longa underground rhizome, inhibits the survival of cancer cells. However, the functional role and mechanism of curcumin in breast cancer remain unclear.Methods: The cell counting kit-8 (CCK-8) assay was performed to examine the effect of curcumin on cell viability in both MDA-MB-453 and MCF-7 cells. Determination of lipid reactive oxygen species (ROS) level, malondialdehyde (MDA) production, and intracellular Fe2+ level was used to evaluate the effect of curcumin on cell ferroptosis. The protein levels were determined by western blot. A xenograft tumor model was employed to verify the antitumorigenic effect of curcumin on breast cancer in vivo.Results: Curcumin treatment significantly suppressed breast cancer cell viability in a dose-dependent manner. Moreover, curcumin triggered ferroptosis by enhancing the levels of lipid ROS, lipid peroxidation end-product MDA accumulation, and intracellular Fe2+. Mechanistically, curcumin administration impeded tumor growth via upregulating solute carrier family 1 member 5 (SLC1A5)-mediated ferroptosis in breast cancer. In vivo experiments showed that curcumin could effectively hamper the growth of tumors without noticeable side effects.Conclusion: We demonstrated that curcumin exhibits anti-tumorigenesis activity in breast cancer by promoting SLC1A5-mediated ferroptosis, providing a potential therapeutic agent for the treatment of breast cancer.

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Danshen Improves Survival of Patients With Breast Cancer and Dihydroisotanshinone I Induces Ferroptosis and Apoptosis of Breast Cancer Cells

Cited by 86 publications

References 40 publications

Dihydrotanshinone I inhibits human glioma cell proliferation via the activation of ferroptosis

Dihydrotanshinone I inhibits human glioma cell proliferation via the activation of ferroptosis

Novel insights on targeting ferroptosis in cancer therapy

Curcumin Suppresses Tumorigenesis via Promoting SLC1A5-mediated Ferroptosis in Breast Cancer

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