8-paradol from ginger exacerbates PINK1/Parkin mediated mitophagy to induce apoptosis in human gastric adenocarcinoma

Wang, Rongbo; Lee, Yeong‐Geun; Dhandapani, Sanjeevram; Baek, Nam‐In; Kim, Kwang Pyo; Cho, Yeong-Eun; Xu, Xingyue; Kim, Yeon-Ju

doi:10.1016/j.phrs.2022.106610

Cited by 14 publications

(14 citation statements)

References 48 publications

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“…Subsequently, the lower the binding ability, the more stable the binding between the ligand and the receptor (the lower the binding energy, the better the binding) in vina docking results. Therefore, among the first 20 compounds, we screened out the compounds with binding energy less than -7.0 kcal/mol by vina ( 22 ), namely, deslanoside ( Figure 10A ), flavitan ( Figure 10C ), ivermectin ( Figure 10E ), and posaconazole ( Figure 10G ), which have strong binding activity with IGF1. The results also show the interaction between these drugs and IGF1.…”

Section: Resultsmentioning

confidence: 99%

Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis

Zhao,

Wang,

Yan

et al. 2023

Front. Immunol.

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Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are downloaded from the Gene Expression Database. Weighted gene co-expression network analysis is used to identify the co-expression modules related to PF and PH. We used the ClueGO software to enrich and analyze the common genes in PF and PH and obtained the protein–protein interaction (PPI) network. Then, the differential genes were screened out in another cohort of PF and PH, and the shared genes were crossed. Finally, RT-PCR verification and immune infiltration analysis were performed on the intersection genes. In the result, the positive correlation module with the highest correlation between PF and PH was determined, and it was found that lymphocyte activation is a common feature of the pathophysiology of PF and PH. Eight common characteristic genes (ACTR2, COL5A2, COL6A3, CYSLTR1, IGF1, RSPO3, SCARNA17 and SEL1L) were gained. Immune infiltration showed that compared with the control group, resting CD4 memory T cells were upregulated in PF and PH. Combining the results of crossing characteristic genes in ImmPort database and RT-PCR, the important gene IGF1 was obtained. Knocking down IGF1 could significantly reduce the proliferation and apoptosis resistance in pulmonary microvascular endothelial cells, pulmonary smooth muscle cells, and fibroblasts induced by hypoxia, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-β1 (TGF-β1), respectively. Our work identified the common biomarkers of PF and PH and provided a new candidate gene for the potential therapeutic targets of PF and PH in the future.

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Section: Resultsmentioning

confidence: 99%

Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis

Zhao,

Wang,

Yan

et al. 2023

Front. Immunol.

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“…The mouse-housed conditions were described as previously. 38 All animal experiments were conducted according to the National Institutes of Health Guide for the care and use of laboratory animals (NIH Publications No. 8023) and the guidelines of Kyung Hee University (KHGASP-21−441, approval date: Sep. 28th, 2021).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Lysine-Rich Polypeptide Modulates Forkhead Box O3 and Phosphoinositide 3-Kinase-Protein Kinase B Pathway To Induce Apoptosis in Breast Cancer

Dhandapani,

Choi,

Chung

et al. 2024

ACS Pharmacol. Transl. Sci.

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The PI3K/AKT/FOXO3 pathway is one of the most frequently involved signaling pathways in cancer, including breast cancer. Therefore, we synthesized a novel lysine-rich polypeptide (Lys-PP) using de novo assembly method and evaluated its anticancer effect. We characterized the structural and physicochemical properties of Lys-PP using various techniques. Later, we used integrated approaches such as in silico, in vitro, and in vivo analysis to confirm the anticancer and therapeutic effect of Lys-PP. First, RNA sequencing suggests Lys-PP disrupted the central carbon metabolic pathway through the modulation of prolactin signaling. Additionally, docking analysis also confirmed the significant association of PI3K/AKT and FOXO3 pathway to induce an apoptotic effect on cancer. Second, Lys-PP exhibited a significant cytotoxicity effect against MDA-MB-231 but no cytotoxic effects on RAW 264.7 and HEK-293, respectively. The cytotoxic effect of Lys-PP-induced apoptosis by an increase in FOXO3a protein expression and a decrease in PI3K/AKT pathway was confirmed by quantitative real-time polymerase chain reaction, immunoblotting, and fluorescent microscopy. Later, immunohistochemistry and hematoxylin and eosin staining on MDA-MD-231 showed increased FOXO3a expression and cell death in the xenograft mice model. Further, liver function, metabolic health, or lipid profile upon Lys-PP showed the absence of significant modulation in the biomarkers except for kidney-related biomarkers. Overall, our comprehensive study provides the first evidence of Lys-PP antibreast cancer action, which could serve as a potential treatment in an alternative or complementary medicine practice.

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“…Natural products, a tremendous trove for drug development, have been shown to exert anticancer effects by regulating diverse programmed cell death (Kandhari et al, 2023;R. Wang, Lee, Dhandapani, et al, 2023;.…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, under near‐infrared light irradiation, pH‐responsive oxazine assemblies triggered ferroptosis in 4T1 cells by enhancing the Fenton reaction, thereby inhibiting tumor growth in vivo (W. Li, Yin, et al, 2023). Natural products, a tremendous trove for drug development, have been shown to exert anticancer effects by regulating diverse programmed cell death (Kandhari et al, 2023; R. Wang, Lee, Dhandapani, et al, 2023; Z. Zhou, Li, et al, 2023). Typically, natural products have a better safety profile than new synthetic compounds.…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis: Potential opportunities for natural products in cancer therapy

Nie,

Shen,

Zhou

et al. 2023

Phytotherapy Research

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Cancer cells often exhibit defects in the execution of cell death, resulting in poor clinical outcomes for patients with many cancer types. Ferroptosis is a newly discovered form of programmed cell death characterized by intracellular iron overload and lipid peroxidation in the cell membrane. Increasing evidence suggests that ferroptosis is closely associated with a wide variety of physiological and pathological processes, particularly in cancer. Notably, various bioactive natural products have been shown to induce the initiation and execution of ferroptosis in cancer cells, thereby exerting anticancer effects. In this review, we summarize the core regulatory mechanisms of ferroptosis and the multifaceted roles of ferroptosis in cancer. Importantly, we focus on natural products that regulate ferroptosis in cancer cells, such as terpenoids, polyphenols, alkaloids, steroids, quinones, and polysaccharides. The clinical efficacy, adverse effects, and drug–drug interactions of these natural products need to be evaluated in further high‐quality studies to accelerate their application in cancer treatment.

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8-paradol from ginger exacerbates PINK1/Parkin mediated mitophagy to induce apoptosis in human gastric adenocarcinoma

Cited by 14 publications

References 48 publications

Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis

Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis

Lysine-Rich Polypeptide Modulates Forkhead Box O3 and Phosphoinositide 3-Kinase-Protein Kinase B Pathway To Induce Apoptosis in Breast Cancer

Ferroptosis: Potential opportunities for natural products in cancer therapy

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