Hyeon Woo Kim

Dongguk University

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Sun Jung Kim

Dongguk University

Hwee Won Ji

Dongguk University

Juyeon Ham

Dongguk University

Dawoon Jeong

Seoul National University

Jae Eun Park

Seoul National University of Science and Technology

Sung Hwan Yun

Dongguk University

Heejoo Kim

Dongguk University

Chun Gwon Park

Sungkyunkwan University

Sang Hyun Sung

Seoul National University

Minjae Baek

National Cancer Center

Cooperative Institutions

Seoul National University

Dongguk University

Chungnam National University

Chungnam National University Hospital

Sungkyunkwan University

Korea Research Institute of Bioscience and Biotechnology

University of Ulsan

National Cancer Center

Kyung Hee University

Korea Institute of Science and Technology

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Lignans from Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidative stress

Bioscience Biotechnology and Biochemistry (2016)

J Kim Heejung Yang Hyeon Woo Kim Hong Pyo Kim Sang Hyun Sung

Bioactivity-guided isolation of Opuntia ficus-indica (Cactaceae) seeds against ethanol-treated primary rat hepatocytes yielded six lignan compounds. Among the isolates, furofuran lignans 4-6, significantly protected rat hepatocytes against ethanol-induced oxidative stress by reducing intracellular reactive oxygen species levels, preserving antioxidative defense enzyme activities, and maintaining the glutathione content. Moreover, 4 dose-dependently induced the heme oxygenase-1 expression in HepG2 cells.

Moraceae

10.1080/09168451.2016.1234930

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Citations (21)

Ginsenoside Rh2 upregulates long noncoding RNA STXBP5-AS1 to sponge microRNA-4425 in suppressing breast cancer cell proliferation

Journal of Ginseng Research (2021)

Jae Eun Park Hyeon Woo Kim Sung Hwan Yun Sun Jung Kim

Ginsenoside Rh2, a major saponin derivative in ginseng extract, is recognized for its anticancer activities. Compared to coding genes, studies on long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) that are regulated by Rh2 in cancer cells, especially on competitive endogenous RNA (ceRNA) are sparse. LncRNAs whose promoter DNA methylation level was significantly altered by Rh2 were screened from methylation array data. The effect of STXBP5-AS1, miR-4425, and RNF217 on the proliferation and apoptosis of MCF-7 breast cancer cells was monitored in the presence of Rh2 after deregulating the corresponding gene. The ceRNA relationship between STXBP5-AS1 and miR-4425 was examined by measuring the luciferase activity of a recombinant luciferase/STXBP5-AS1 plasmid construct in the presence of mimic miR-4425. Inhibition of STXBP5-AS1 decreased apoptosis but stimulated growth of the MCF-7 cells, suggesting tumor-suppressive activity of the lncRNA. MiR-4425 was identified to have a binding site on STXBP5-AS1 and proven to be downregulated by STXBP5-AS1 as well as by Rh2. In contrast to STXBP5-AS1, miR-4425 showed pro-proliferation activity by inducing a decrease in apoptosis but increased growth of the MCF-7 cells. MiR-4425 decreased luciferase activity from the luciferase/STXBP5-AS1 construct by 26%. Screening the target genes of miR-4425 and Rh2 revealed that Rh2, STXBP5-AS1, and miR-4425 consistently regulated tumor suppressor RNF217 at both the RNA and protein level. LncRNA STXBP5-AS1 is upregulated by Rh2 via promoter hypomethylation and acts as a ceRNA, sponging the oncogenic miR-4425. Therefore, Rh2 controls the STXBP5-AS1/miR-4425/RNF217 axis to suppress breast cancer cell growth.

Competing Endogenous RNA

10.1016/j.jgr.2021.08.006

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Ovarian Absorption and Systemic Bioavailability Study of Paeoniflorin Solubilized with L-Lysine

Yakhak Hoeji (2023)

Ye Jin Hwang Ah Rum Kim Hyeon Woo Kim Jae Seon Kang

Menopause refers to the period in a woman’s life when ovarian function declines, leading to a cessation of ovulation and a significant hormonal shift. Commonly associated symptoms include facial flushing, sleep disturbances, fatigue, and depression. These symptoms are typically treated with hormone therapy, although there is concern about the increased risk of endometrial cancer, cardiovascular disease, and breast cancer associated with excessive estrogen use. This has led to a growing interest in natural remedies as an alternative approach. Paeoniflorin is a pharmacologically active compound found in Paeonia lactiflora, one of the major components of this plant. Paeonia lactiflora has been traditionally used to treat women’s health issues, but there is currently insufficient research in this area compared to its historical use. Moreover, there is a lack of studies on ovarian absorption rates, prompting the present study. In this research, paeoniflorin was solubilized using L-Lysine, and its ovarian absorption rate and overall bioavailability were compared to the conventional extract. The results demonstrated a 58.5% increase in ovarian absorption when solubilized with L-Lysine. In terms of overall bioavailability, the area under the curve (AUC) value for oral administration was 3122.66 ng·hr/mL, whereas the AUC value for intravenous injection was 4191.20 ng·hr/mL. These findings suggest the potential of L-Lysinesolubilized paeoniflorin as an effective treatment for menopausal symptoms, offering a promising natural alternative to hormone therapy.

Paeoniflorin

Paeonia lactiflora

10.17480/psk.2023.67.6.372

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Salvia miltiorrhiza extract protects white matter and the hippocampus from damage induced by chronic cerebral hypoperfusion in rats

BMC Complementary and Alternative Medicine (2015)

Min‐Soo Kim Ji Hye Bang Jun Lee Hyeon Woo Kim Sang Hyun Sung

Salvia miltiorrhiza (SM), an herbal plant, is traditionally used in the treatment of cardiovascular and cerebrovascular diseases in Asian countries. SM has multiple biological effects including anti-inflammatory activity. The present study is aimed at investigating the effects of SM extract in rats with chronic cerebral hypoperfusion.Chronic cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral common carotid artery occlusion (BCCAo). The rats were divided into 3 groups: sham-control, BCCAo treated with vehicle, and BCCAo treated with SM extract. Vehicle or SM extract (200 mg/kg) were administered daily by oral gavage beginning on day 21 after BCCAo and continuing to day 42. Immunohistochemical analyses were used to measure Iba-1-positive microglia and myelin basic protein (MBP) in white matter and hippocampal tissue. In addition, the expression levels of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, and the toll-like receptor (TLR) pathway in the hippocampus, were analyzed by western blot.Administration of SM extract attenuated the activation of microglial cells in the white matter and hippocampus after BCCAo. SM extract also prevented neuroinflammation after BCCAo by reducing hippocampal levels of TNF-α, IL-1β, and IL-6, and increasing the reduced levels of MBP in the white matter and hippocampus. Further, the administration of SM extract alleviated the up-regulation of hippocampal TLR4 and myeloid differentiation primary response gene 88 (MyD88) in rats with chronic BCCAo.Our findings suggest that SM may be a promising therapeutic candidate in vascular dementia because of its protective effects against damage to the white matter and hippocampus after BCCAo.

Salvia miltiorrhiza

Cerebral Hypoperfusion

10.1186/s12906-015-0943-6

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Citations (29)

Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells

Biomolecules (2021)

Hee Joo Kim Hwee Won Ji Hyeon Woo Kim Sung Hwan Yun Jae Eun Park

Ginsenoside Rg3 exerts antiproliferation activity on cancer cells by regulating diverse noncoding RNAs. However, little is known about the role of long noncoding RNAs (lncRNAs) or their relationship with competitive endogenous RNA (ceRNA) in Rg3-treated cancer cells. Here, a lncRNA (ATXN8OS) was found to be downregulated via Rg3-mediated promoter hypermethylation in MCF-7 breast cancer cells. SiRNA-induced downregulation of ATXN8OS decreased cell proliferation but increased apoptosis, suggesting that the noncoding RNA possessed proproliferation activity. An in silico search for potential ATXN8OS-targeting microRNAs (miRs) identified a promising candidate (miR-424-5p) based on its high binding score. As expected, miR-424-5p suppressed proliferation and stimulated apoptosis of the MCF-7 cells. The in silico miR-target-gene prediction identified 200 potential target genes of miR-424-5p, which were subsequently narrowed down to seven that underwent hypermethylation at their promoter by Rg3. Among them, three genes (EYA1, DACH1, and CHRM3) were previously known oncogenes and were proven to be oppositely regulated by ATXN8OS and miR-424-5p. When taken together, Rg3 downregulated ATXN8OS that inhibited the tumor-suppressive miR-424-5p, leading to the downregulation of the oncogenic target genes.

Competing Endogenous RNA

10.3390/biom11010118

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Citations (23)

Cold Atmospheric Plasma Restores Paclitaxel Sensitivity to Paclitaxel-Resistant Breast Cancer Cells by Reversing Expression of Resistance-Related Genes

Cancers (2019)

Sung-Bin Park Heejoo Kim Hwee Won Ji Hyeon Woo Kim Sung Hwan Yun

Paclitaxel (Tx) is a widely used therapeutic chemical for breast cancer treatment; however, cancer recurrence remains an obstacle for improved prognosis of cancer patients. In this study, cold atmospheric plasma (CAP) was tested for its potential to overcome the drug resistance. After developing Tx-resistant MCF-7 (MCF-7/TxR) breast cancer cells, CAP was applied to the cells, and its effect on the recovery of drug sensitivity was assessed in both cellular and molecular aspects. Sensitivity to Tx in the MCF-7/TxR cells was restored up to 73% by CAP. A comparison of genome-wide expression profiles between the TxR cells and the CAP-treated cells identified 49 genes that commonly appeared with significant changes. Notably, 20 genes, such as KIF13B, GOLM1, and TLE4, showed opposite expression profiles. The protein expression levels of selected genes, DAGLA and CEACAM1, were recovered to those of their parental cells by CAP. Taken together, CAP inhibited the growth of MCF-7/TxR cancer cells and recovered Tx sensitivity by resetting the expression of multiple drug resistance-related genes. These findings may contribute to extending the application of CAP to the treatment of TxR cancer.

MCF-7

10.3390/cancers11122011

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Citations (38)

ELOVL2-AS1 suppresses tamoxifen resistance by sponging miR-1233-3p in breast cancer

Epigenetics (2023)

Hyeon Woo Kim Minjae Baek Sanghyun Jung S.Y. Jang Hyeonjin Lee

Tamoxifen (Tam) has long been a top treatment option for breast cancer patients, but the challenge of eliminating cancer recurrence remains. Here, we identify a signalling pathway involving ELOVL2, ELOVL2-AS1, and miR-1233-3p, which contributes to drug resistance in Tam-resistant (TamR) breast cancer. ELOVL2-AS1, a long noncoding RNA, was significantly upregulated by its antisense gene, ELOVL2, which is known to be downregulated in TamR cells. Additionally, ELOVL2-AS1 underwent the most hypermethylation in MCF-7/TamR cells. Furthermore, patients with breast cancer who developed TamR during chemotherapy had significantly lower expression of ELOVL2-AS1 compared to those who responded to Tam. Ectopic downregulation of ELOVL2-AS1 by siRNA both stimulated cancer cell growth and deteriorated TamR. We also found that ELOVL2-AS1 sponges miR-1233-3p, which has pro-proliferative activity and elevates TamR, leading to the activation of potential target genes, such as MYEF2, NDST1, and PIK3R1. These findings suggest that ELOVL2-AS1, in association with ELOVL2, may contribute to the suppression of drug resistance by sponging miR-1233-3p in breast cancer.

10.1080/15592294.2023.2276384

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Ginsenoside Rh2 Suppresses Breast Cancer Cell Proliferation by Epigenetically Regulating the Long Noncoding RNA C3orf67-AS1

The American Journal of Chinese Medicine (2019)

Dawoon Jeong Juyeon Ham Chun Gwon Park Hyeon Woo Kim Heejoo Kim

Ginsenoside Rh2, a major bioactive ingredient abundant in red ginseng, has an antiproliferative effect on various cancer cells. In this study, we report a novel long noncoding RNA, C3orf67-AS1, which was identified as being hypermethylated at a CpG site of the promoter by Rh2 in MCF-7 cancer cells. Rh2-induced hypermethylation was responsible for the lower gene expression; the expression was recovered following treatment with a methyltransferase inhibitor, 5-aza-2 ′ -deoxycytidine. When C3orf67-AS1 was downregulated by a siRNA, the cell growth rate was decreased, demonstrating the RNA’s oncogenic activity. Accordingly, breast cancer patients showed a lower methylation and higher expression level of C3orf67-AS1. Within 800 kb flanking C3orf67-AS1 on the chromosome, eight genes were found, and four genes including C3orf67 (the sense strand gene of C3orf67-AS1) were downregulated by Rh2. In particular, C3orf67 was downregulated when C3orf67-AS1 was suppressed by a siRNA; however, the expression of C3orf67-AS1 was not affected by C3orf67. Taken together, this study identifies a novel noncoding RNA, C3orf67-AS1, of which the expression could be suppressed by Rh2 via promoter methylation, thereby mediating the anti-proliferative effect of the ginsenoside.

CpG site

DNA methyltransferase

10.1142/s0192415x19500848

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Citations (29)

Isolation and structure elucidation of (−)-idescarparide, a new spiro compound from Idesia polycarpa

Tetrahedron Letters (2014)

Tae‐Bum Kim Hyeon Woo Kim Mina Lee Hyang Hwa Lee Seung Hyun Kim

Isolation

10.1016/j.tetlet.2014.08.010

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Citations (6)

Ginsenoside Rh2 Regulates the CFAP20DC-AS1/MicroRNA-3614-3p/BBX and TNFAIP3 Axis to Induce Apoptosis in Breast Cancer Cells

The American Journal of Chinese Medicine (2022)

Jae Eun Park Hwee Won Ji Hyeon Woo Kim Minjae Baek Sanghyun Jung

While a number of coding genes have explained the anticancer activity of ginsenoside Rh2, little is known about noncoding RNAs. This study was performed to elucidate the regulatory activity of long noncoding RNA (lncRNA) CFAP20DC-AS1, which is known to be downregulated by Rh2. MiR-3614-3p, which potentially binds CFAP20DC-AS1, was screened using the LncBase Predicted program, and the binding was verified by assaying the luciferase activity of a luciferase/lncRNA recombinant plasmid construct. The competitive endogenous RNA (ceRNA) relationship of the two RNAs was further validated by quantitative PCR after deregulation of each RNA using siRNA. The effect of miRNA and target genes on the MCF-7 cancer cell growth was determined by monitoring proliferation and apoptosis in the presence of Rh2 after deregulating the corresponding gene. The miRNA decreased the luciferase activity of the luciferase/CFAP20DC-AS1 fusion vector, confirming the binding. SiRNA-based deregulation of CFAP20DC-AS1 attenuated the expression of miR-3614-3p and vice versa. In contrast to CFAP20DC-AS1, miR-3614-3p was upregulated by Rh2, inhibiting proliferation but stimulating apoptosis of the MCF-7 cells. Target genes of miR-3614-3p, BBX and TNFAIP3, were downregulated by Rh2 and the miRNA but upregulated by the lncRNA. Rh2 inhibits CFAP20DC-AS1, which obscures the association of the lncRNA with miR-3614-3p, resulting in the suppression of oncogenic BBX and TNFAIP3. Taken together, the Rh2/CFAP20DC-AS1/miR-3614-3p/target gene axis contributes to the antiproliferation activity of Rh2 in cancer cells.

Competing Endogenous RNA

10.1142/s0192415x22500720

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Citations (9)