Anticancer effects of aloe-emodin from Rheum undulatum L. through activation of the p53 pathway in human prostate cancer cells Nguyen Khoi Song Tran, Nhu Quynh Nguyen, Sullim Lee, Seung Hyun Kim, Daesik Jeong, et al. Applied Biological Chemistry, 2024 Aloe-emodin, an anthraquinone compound naturally derived from Rheum undulatum L., has gained extensive research attention owing to its various pharmacological effects, including its potential as an anticancer, antivirus, anti-inflammatory, antibacterial, and anti-parasitic agent. It has demonstrated notable inhibitory effects against various types of cancer and cancer cells. Prostate cancer is among the most commonly identified cancers globally and remains a leading cause of cancer-associated deaths in men, often presenting challenges in early detection due to its asymptomatic nature during initial stages. The aim of present study was to determine the biological activity of aloe-emodin obtained from Rheum undulatum L. involving activation of the p53-dependent pathway in certain human prostate cancer cell lines. We explored the mechanisms underlying the anticancer effects of aloe-emodin using LNCaP cells, which include p53-wild type and phosphatase and tensin homolog-deficient mutated genes, a widely studied model in genomic research. Aloe-emodin induced apoptosis in LNCaP cells through several mechanisms, including upregulation of the cleavage of caspase-8 (a cross-linked promoter of cell death signals), phosphorylation of p53 at serine 15, DNA fragmentation, cleavage of poly [ADP-ribose] polymerase, and promotion of cell death. These findings strongly indicated that aloe-emodin's anticancer properties in human prostate cancer involve the activation of p53-induced cellular senescence. Conclusively, the findings of this study imply that aloe-emodin extracted from Rheum undulatum L. is a potential therapeutic compound for adjuvant chemotherapy that induces apoptosis and pyroptosis, an innate immune response, in preventing the progression of precancerous lesions in patients with prostate cancer.
Aloe-Emodin Isolated from Rheum Undulatum L. Regulates Cell Cycle Distribution and Cellular Senescence in Human Prostate Cancer LNCaP Cells Mei Tong He, Quynh Nhu Nguyen, Eun Ju Cho, Seung Hyun Kim, SeonJu Park, et al. Journal of Dietary Supplements, 2024 Senescence can promote hyperplastic pathologies, such as cancer. Prostate cancer is the second most common type of cancer in men. The p21-mediate cellular senescence, facilitated through the tumor suppressor p53-dependent pathway, is considered the primary mechanism for cancer treatment. Aloe-emodin, has been reported to exert anticancer effects in various types of cancers. This study aimed to investigate the bioactivity of aloe-emodin in LNCaP cells via the activation of p21-mediated cellular senescence. Aloe-emodin treatment increased the percentage of cells in the G1 phase while decreasing the percentage in the S phase. This effect was reflected in the expression levels of proteins associated with cell cycle progression, such as p21CIP, retinoblastoma protein, and cyclin-dependent kinase2/4 in LNCaP cells. However, aloe-emodin-treated LNCaP cells did not induce cell cycle arrest at G2/M checkpoint. Moreover, increased senescence-associated-galactosidase activity was observed in a dose-dependent manner following treatment with aloe-emodin. Aloe-emodin also induced DNA damage by modulating the expression of histone H2AX and lamin B1. Furthermore, aloe-emodin inhibited the proliferation of LNCaP cells, contrasting with the exponential growth observed in the nontreated cells. Importantly, this inhibition did not impact the immune system, as evidenced by the increased proliferation of splenocytes isolated from mice. These findings provide preliminary evidence of the anticancer effect of aloe-emodin in LNCaP cells, necessitating further investigations into the underlying mechanisms in vivo and human subjects.
Global Natural Products Social (GNPS)-Based Molecular-Networking-Guided Isolation of Phenolic Compounds from Ginkgo biloba Fruits and the Identification of Estrogenic Phenolic Glycosides Chen Huo, Quynh Nhu Nguyen, Akida Alishir, Moon-Jin Ra, Sang-Mi Jung, et al. Plants, 2023 Ginkgo biloba L. stands as one of the oldest living tree species, exhibiting a diverse range of biological activities, including antioxidant, neuroprotective, anti-inflammatory, and cardiovascular activities. As part of our ongoing discovery of novel bioactive components from natural sources, we directed our focus toward the investigation of potential bioactive compounds from G. biloba fruit. The profiles of its chemical compounds were examined using a Global Natural Products Social (GNPS)-based molecular networking analysis. Guided by this, we successfully isolated and characterized 11 compounds from G. biloba fruit, including (E)-coniferin (1), syringin (2), 4-hydroxybenzoic acid 4-O-β-D-glucopyranoside (3), vanillic acid 4-O-β-D-glucopyranoside (4), syringic acid 4-O-β-D-glucopyranoside (5), (E)-ferulic acid 4-O-β-D-glucoside (6), (E)-sinapic acid 4-O-β-D-glucopyranoside (7), (1′R,2′S,5′R,8′S,2′Z,4′E)-dihydrophaseic acid 3′-O-β-D-glucopyranoside (8), eucomic acid (9), rutin (10), and laricitrin 3-rutinoside (11). The structural identification was validated through a comprehensive analysis involving nuclear magnetic resonance (NMR) spectroscopic data and LC/MS analyses. All isolated compounds were evaluated using an E-screen assay for their estrogen-like effects in MCF-7 cells. As a result, compounds 2, 3, 4, 8, and 9 promoted cell proliferation in MCF-7 cells, and these effects were mitigated by the ER antagonist, ICI 182,780. In particular, cell proliferation increased most significantly to 140.9 ± 6.5% after treatment with 100 µM of compound 2. The mechanism underlying the estrogen-like effect of syringin (2) was evaluated using a Western blot analysis to determine the expression of estrogen receptor α (ERα). We found that syringin (2) induced an increase in the phosphorylation of ERα. Overall, these experimental results suggest that syringin (2) can potentially aid the control of estrogenic activity during menopause.
Estrogenic activity of freeze-dried silkworm extracts through the activation of estrogen receptors in MCF-7 cells Sullim Lee, Quynh Nhu Nguyen, Sung Jin Kim, Joohwan Lee, Myoung-Sook Shin Applied Biological Chemistry, 2022 Silkworm is an insect that feeds on mulberry leaves only, and silkworm powder has been reported to have antioxidant, hypoglycemic, and anticholesterol activities. In this study, we measured the content of 1-deoxynojirimycin (1-DNJ) in 24 different extracts from silkworm cocoons and also investigated the estrogenic activities of these extracts and their effects on the activation of intracellular signaling pathways in MCF-7 breast cancer cells. Among the 24 silkworm extracts, relatively high 1-DNJ content and estrogenic activity were shown by Extract 11 (30E3H20-1), which was prepared by a single extraction of silkworm powder with 20 times the volume of 30% ethanol against each powder weight for 3 h. The estrogen receptor activity of this extract was confirmed based on its promoting effects on the phosphorylation of the estrogen receptor α (ERα) and mRNA expression of the ESR1 and ESR2 genes. In addition, treatment with Extract 11 (30E3H20-1) increased the phosphorylation of AKT, p38, and JNK, which are downstream proteins of ERα. Based on our findings, a silkworm extract could be developed as a natural estrogen supplement in the future.
Estrogenic Activity of 4-Hydroxy-Benzoic Acid from Acer tegmentosum via Estrogen Receptor α-Dependent Signaling Pathways Quynh Nhu Nguyen, Seoung Rak Lee, Baolo Kim, Joo-Hyun Hong, Yoon Seo Jang, et al. Plants, 2022 Acer tegmentosum, a deciduous tree belonging to Aceraceae, has been used in traditional oriental medicine for treating hepatic disorders, such as hepatitis, cirrhosis, and liver cancer. We evaluated the estrogen-like effects of A. tegmentosum using an estrogen receptor (ER)-positive breast cancer cell line, namely MCF-7, to identify potential phytoestrogens and found that an aqueous extract of A. tegmentosum promoted cell proliferation in MCF-7 cells. Five phenolic compounds (1–5) were separated and identified from the active fraction using bioassay-guided fractionation of crude A. tegmentosum extract and phytochemical analysis. The chemical structures of the compounds were characterized as vanillic acid (1), 4-hydroxy-benzoic acid (2), syringic acid (3), isoscopoletin (4), and (E)-ferulic acid (5) based on the analysis of their nuclear magnetic resonance spectra and liquid chromatography-mass spectrometry data. All five compounds were evaluated using an E-screen assay for their estrogen-like effects on MCF-7 cells. Among the tested compounds, only 4-hydroxy-benzoic acid (2) promoted the proliferation of MCF-7 cells, which was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of 4-hydroxy-benzoic acid (2) was evaluated via western blotting analysis to determine the expression levels of extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), serine/threonine kinase (AKT), and ERα. Our results demonstrated that 4-hydroxy-benzoic acid (2) induced the increase in the protein expression levels of p-ERK, p-AKT, p-PI3K, and p-Erα, concentration dependently. Collectively, these experimental results suggest that 4-hydroxy-benzoic acid (2) is responsible for the estrogen-like effects of A. tegmentosum and may potentially aid in the control of estrogenic effects during menopause.
Beneficial role of Boehmeria nivea in health and phytochemical constituents Jungwon Choi, Quynh Nhu Nguyen, Ji Yun Baek, Da‐Eun Cho, Ki Sung Kang, et al. Journal of Food Biochemistry, 2022 The leaf and stem extracts of Boehmeria nivea (BN) collected from three different regions in Korea were screened for their antioxidant, neuroprotective, estrogenic, insulin secretion, and α-glucosidase inhibitory activity. We also examined whether BN extracts regulate cancer cell growth, inflammatory-related gene expression, and lipid accumulation in cellular system. Leaf extracts possessed greater antioxidant, anti-proliferative in cancer cells, neuroprotective, estrogenic activity, and inhibitory effect on pro-inflammatory gene expression than stem extracts. Leaf and stem extracts inhibited lipid accumulation in three T3-L1 adipocytes but did not affect glucose-stimulated insulin secretion in INS-1 cells. We isolated and identified the phytochemical constituents in the n-butanol and ethyl acetate fractions of BN leaves by combining silica gel column chromatography with mass spectrometry and 1 H- and 13 C-NMR analysis. The active compounds (caffeic acid, isoquercitrin, p-coumaric acid, and rutin) exhibited ABTS and DPPH radical scavenging activity, which may contribute to the biological activities of BN leaf extract. An analytical method was developed to quantify marker compounds for the discrimination of BN collected from different regions. Our results support the use of this analysis method for accurate identification and quantification of marker compounds in BN for the development of functional foods. PRACTICAL APPLICATIONS: Boehmeria nivea (BN) has been used as a raw material for the textile industry or traditional herbal medicine. The current study established the biological activities and active components of BN. Our results showed that BN leaf and stem extracts exhibit antioxidant, neuroprotective, and estrogenic activity. BN leaf extract also inhibited cancer cell growth, inflammatory mediators and cytokines production, and lipid accumulation in vitro. Moreover, the bioactive compounds, such as caffeic acid, isoquercitrin, p-coumaric acid, and rutin, exert ABTS and DPPH radical scavenging activities. Therefore, BN could potentially be a promising source of bioactive phytochemicals for the development of functional foods or drugs.
The Ameliorating Effect of Lizhong-Tang on Antibiotic-Associated Imbalance in the Gut Microbiota in Mouse Hye-Ri Ahn, Do Hwi Park, Myoung-Sook Shin, Quynh Nhu Nguyen, Jun Yeon Park, et al. Applied Sciences Switzerland, 2022 Some herbal medicines have anti-inflammatory and anti-diarrheal effects. This study analyzed the modulating effect of gut microbiota of anti-inflammatory herbal medicines on antibiotic-associated diarrhea (AAD). The anti-inflammatory effects of 10 herbal medicines and Lizhong-tang active compounds were studied by measuring the nitric oxide production in an in vitro experiment. This was followed by an in vivo experiment in which the anti-diarrheal effects of Lizhong-tang and Magnolia officinalis in a lincomycin-induced AAD mouse model were measured. Changes in the intestinal microflora were observed using terminal restriction fragment length polymorphism analysis. Both Lizhong-tang and M. officinalis were effective against AAD, with Lizhong-tang’s anti-diarrheal effects being particularly effective. In addition, the active compounds of Lizhong-tang, liquiritin and 6-gingerol, inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2, thus showing an anti-inflammatory effect. Gut microbiota analysis showed that Lizhong-tang could alter the composition of the gut microbiota and ameliorated imbalance in the gut microbiota in a lincomycin-induced AAD mouse model.
Anticancer effects of aloe-emodin from Rheum undulatum L. through activation of the p53 pathway in human prostate cancer cells NKS Tran, NQ Nguyen, S Lee, SH Kim, D Jeong, E Seo, JJ Park, J Cho, ... Applied Biological Chemistry 67 (1), 102 , 2024 2024 Citations: 9
Initial Phenotypic Characterization of Anti-SEM4A CAR T Cells P Celichowski, QN Nguyen, S Charvatova, M Durech, J Kotulova, ... Blood 144, 7145 , 2024 2024
Aloe-Emodin Isolated from Rheum Undulatum L. Regulates Cell Cycle Distribution and Cellular Senescence in Human Prostate Cancer LNCaP Cells MT He, QN Nguyen, EJ Cho, SH Kim, SJ Park, JY Park, S Lee, KS Kang Journal of Dietary Supplements 21 (3), 389-407 , 2024 2024 Citations: 10
Global Natural Products Social (GNPS)-Based Molecular-Networking-Guided Isolation of Phenolic Compounds from Ginkgo biloba Fruits and the Identification of … C Huo, QN Nguyen, A Alishir, MJ Ra, SM Jung, JN Yu, HJ Gwon, KS Kang, ... Plants 12 (23), 3970 , 2023 2023 Citations: 21
Mass production of entomopathogenic fungi Purpureocillium lilacinum PL1 as a biopesticide for the management of Amrasca devastans (Hemiptera: Cicadellidae … H Nguyen Thi, QN Nguyen, NQ Dang Thi, NL Nguyen, AD Do Egyptian Journal of Biological Pest Control 33 (1), 85 , 2023 2023 Citations: 12
Estrogenic Activity of 4-Hydroxy-Benzoic Acid from Acer tegmentosum via Estrogen Receptor α-Dependent Signaling Pathways QN Nguyen, SR Lee, B Kim, JH Hong, YS Jang, DE Lee, C Pang, ... Plants 11 (23), 3387 , 2022 2022 Citations: 15
Beneficial role of Boehmeria nivea in health and phytochemical constituents J Choi, QN Nguyen, JY Baek, DE Cho, KS Kang, DH Hahm, TW Jang, ... Journal of Food Biochemistry 46 (12), e14474 , 2022 2022 Citations: 9
Chemical constituents from Neopestalotiopsis clavispora culture medium with estrogenic effects in MCF-7 cells H Kwon, QN Nguyen, SM Ryu, J Kwon, S Park, Y Guo, BY Hwang, JH Yim, ... Phytochemistry Letters 52, 134-137 , 2022 2022 Citations: 5
Estrogenic activity of freeze-dried silkworm extracts through the activation of estrogen receptors in MCF-7 cells S Lee, QN Nguyen, SJ Kim, J Lee, MS Shin Applied Biological Chemistry 65 (1), 43 , 2022 2022 Citations: 4
The Ameliorating Effect of Lizhong-Tang on Antibiotic-Associated Imbalance in the Gut Microbiota in Mouse HR Ahn, DH Park, MS Shin, QN Nguyen, JY Park, DW Kim, KS Kang, ... Applied Sciences 12 (14), 6943 , 2022 2022 Citations: 6
Regulation of appetite-related neuropeptides by Panax ginseng: A novel approach for obesity treatment HM Phung, D Jang, TA Trinh, D Lee, QN Nguyen, CE Kim, KS Kang Journal of Ginseng Research 46 (4), 609-619 , 2022 2022 Citations: 23
A new α -pyrone from Arthrinium pseudosinense culture medium and its estrogenic activity in MCF-7 cells H Kwon, QN Nguyen, MW Na, KH Kim, Y Guo, JH Yim, SH Shim, JJ Kim, ... The Journal of Antibiotics 74 (12), 893-897 , 2021 2021 Citations: 9
Chemical constituents from basidiomycete Basidioradulum radula culture medium and their cytotoxic effect on human prostate cancer DU-145 cells SM Ryu, QN Nguyen, S Lee, H Kwon, J Kwon, H Lee, SL Kwon, J Lee, ... Bioorganic Chemistry 114, 105064 , 2021 2021 Citations: 3
Identification of the Active Ingredient and Beneficial Effects of Vitex rotundifolia Fruits on Menopausal Symptoms in Ovariectomized Rats JH Lee, S Lee, QN Nguyen, HM Phung, MS Shin, JY Kim, H Choi, ... Biomolecules 11 (7), 1033 , 2021 2021 Citations: 15
Preventive Effects of Anthraquinones Isolated from an Endophytic Fungus, Colletotrichum sp. JS-0367 in Tumor Necrosis Factor-α-Stimulated Damage of Human … S Lee, QN Nguyen, HM Phung, SH Shim, D Kim, GS Hwang, KS Kang Antioxidants 10 (2), 200 , 2021 2021 Citations: 13
Protective effect of shikimic acid against cisplatin-induced renal injury: in vitro and in vivo studies J Lee, QN Nguyen, JY Park, S Lee, GS Hwang, N Yamabe, S Choi, ... Plants 9 (12), 1681 , 2020 2020 Citations: 23
MOST CITED SCHOLAR PUBLICATIONS
Regulation of appetite-related neuropeptides by Panax ginseng: A novel approach for obesity treatment HM Phung, D Jang, TA Trinh, D Lee, QN Nguyen, CE Kim, KS Kang Journal of Ginseng Research 46 (4), 609-619 , 2022 2022 Citations: 23
Protective effect of shikimic acid against cisplatin-induced renal injury: in vitro and in vivo studies J Lee, QN Nguyen, JY Park, S Lee, GS Hwang, N Yamabe, S Choi, ... Plants 9 (12), 1681 , 2020 2020 Citations: 23
Global Natural Products Social (GNPS)-Based Molecular-Networking-Guided Isolation of Phenolic Compounds from Ginkgo biloba Fruits and the Identification of … C Huo, QN Nguyen, A Alishir, MJ Ra, SM Jung, JN Yu, HJ Gwon, KS Kang, ... Plants 12 (23), 3970 , 2023 2023 Citations: 21
Estrogenic Activity of 4-Hydroxy-Benzoic Acid from Acer tegmentosum via Estrogen Receptor α-Dependent Signaling Pathways QN Nguyen, SR Lee, B Kim, JH Hong, YS Jang, DE Lee, C Pang, ... Plants 11 (23), 3387 , 2022 2022 Citations: 15
Identification of the Active Ingredient and Beneficial Effects of Vitex rotundifolia Fruits on Menopausal Symptoms in Ovariectomized Rats JH Lee, S Lee, QN Nguyen, HM Phung, MS Shin, JY Kim, H Choi, ... Biomolecules 11 (7), 1033 , 2021 2021 Citations: 15
Preventive Effects of Anthraquinones Isolated from an Endophytic Fungus, Colletotrichum sp. JS-0367 in Tumor Necrosis Factor-α-Stimulated Damage of Human … S Lee, QN Nguyen, HM Phung, SH Shim, D Kim, GS Hwang, KS Kang Antioxidants 10 (2), 200 , 2021 2021 Citations: 13
Mass production of entomopathogenic fungi Purpureocillium lilacinum PL1 as a biopesticide for the management of Amrasca devastans (Hemiptera: Cicadellidae … H Nguyen Thi, QN Nguyen, NQ Dang Thi, NL Nguyen, AD Do Egyptian Journal of Biological Pest Control 33 (1), 85 , 2023 2023 Citations: 12
Aloe-Emodin Isolated from Rheum Undulatum L. Regulates Cell Cycle Distribution and Cellular Senescence in Human Prostate Cancer LNCaP Cells MT He, QN Nguyen, EJ Cho, SH Kim, SJ Park, JY Park, S Lee, KS Kang Journal of Dietary Supplements 21 (3), 389-407 , 2024 2024 Citations: 10
Anticancer effects of aloe-emodin from Rheum undulatum L. through activation of the p53 pathway in human prostate cancer cells NKS Tran, NQ Nguyen, S Lee, SH Kim, D Jeong, E Seo, JJ Park, J Cho, ... Applied Biological Chemistry 67 (1), 102 , 2024 2024 Citations: 9
Beneficial role of Boehmeria nivea in health and phytochemical constituents J Choi, QN Nguyen, JY Baek, DE Cho, KS Kang, DH Hahm, TW Jang, ... Journal of Food Biochemistry 46 (12), e14474 , 2022 2022 Citations: 9
A new α -pyrone from Arthrinium pseudosinense culture medium and its estrogenic activity in MCF-7 cells H Kwon, QN Nguyen, MW Na, KH Kim, Y Guo, JH Yim, SH Shim, JJ Kim, ... The Journal of Antibiotics 74 (12), 893-897 , 2021 2021 Citations: 9
The Ameliorating Effect of Lizhong-Tang on Antibiotic-Associated Imbalance in the Gut Microbiota in Mouse HR Ahn, DH Park, MS Shin, QN Nguyen, JY Park, DW Kim, KS Kang, ... Applied Sciences 12 (14), 6943 , 2022 2022 Citations: 6
Chemical constituents from Neopestalotiopsis clavispora culture medium with estrogenic effects in MCF-7 cells H Kwon, QN Nguyen, SM Ryu, J Kwon, S Park, Y Guo, BY Hwang, JH Yim, ... Phytochemistry Letters 52, 134-137 , 2022 2022 Citations: 5
Estrogenic activity of freeze-dried silkworm extracts through the activation of estrogen receptors in MCF-7 cells S Lee, QN Nguyen, SJ Kim, J Lee, MS Shin Applied Biological Chemistry 65 (1), 43 , 2022 2022 Citations: 4
Chemical constituents from basidiomycete Basidioradulum radula culture medium and their cytotoxic effect on human prostate cancer DU-145 cells SM Ryu, QN Nguyen, S Lee, H Kwon, J Kwon, H Lee, SL Kwon, J Lee, ... Bioorganic Chemistry 114, 105064 , 2021 2021 Citations: 3
Initial Phenotypic Characterization of Anti-SEM4A CAR T Cells P Celichowski, QN Nguyen, S Charvatova, M Durech, J Kotulova, ... Blood 144, 7145 , 2024 2024
