CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Xinyu Qian,Lin Zhu,Mengzhen Xu,Haoli Liu,Xinyan Yu,Qiuyue Shao,Jing Qin
Small cell lung cancer (SCLC) is a subtype of lung cancer with a very poor overall survival rate due to its extremely high proliferation and metastasis predilection. Shikonin is an active ingredient extracted from the roots of Lithospermum erythrorhizon, and exerts multiple anti-tumor functions in many cancers. In the present study, the role and underlying mechanism of shikonin in SCLC were investigated for the first time. We found that shikonin effectively suppressed cell proliferation , apoptosis , migration, invasion, and colony formation and slightly induced apoptosis in SCLC cells. Further experiment indicated the shikonin could also induced ferroptosis in SCLC cells. Shikonin treatment effectively suppressed the activation of ERK, the expression of ferroptosis inhibitor GPX4 , and elevated the level of 4-HNE, a biomarker of ferroptosis. Both total ROS and lipid ROS were increased, while the GSH levels were decreased in SCLC cells after shikonin treatment. More importantly, our data identified that the function of shikonin was dependent on the up-regulation of ATF3 by performing rescue experiments using shRNA to silence the expression of ATF3, especially in the total and lipid ROS accumulaiton. Xenograft model was established using SBC-2 cells, and the results revealed that shikonin also significantly inhibited tumor growth by inducing ferroptosis. Finally, our data further confirmed that shikonin activated ATF3 transcription by impairing the recruitment of HDAC1 mediated by c-myc on the ATF3 promoter , and subsequently elevating of histone acetylation . Our data documented that shikonin suppressed SCLC by inducing ferroptosis in a ATF3-dependent manner. Shikonin upregulated the expression of ATF3 expression via promoting the histone acetylation by inhibiting c-myc-mediated HDAC1 binding on ATF3 promoter.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Xin-Yao Li,Bang-Yin Tan,Yue Zhang,Yan-Lin Lv,Yun-Li Zhao,Xiao-Dong Luo
Ethnopharmacological relevance Stemona sessilifolia (Miq.) Miq. has been employed in traditional medicine for its potential renal benefits, including anti-edema, diuretic, and anti-jaundice properties. However, the renoprotective effects related to these traditional uses remain to be fully elucidated. Aim of the study : To investigate the therapeutic efficacy of S . sessilifolia against hyperuricemic nephropathy and elucidate its underlying signaling pathway. Materials and methods A hyperuricemic nephropathy mouse model, induced by potassium oxonate and hypoxanthine, was employed to evaluate the renal protection of the extract of S. sessilifolia through biochemical tests and histopathological observation. Transcriptomic analysis was applied to explore potential signaling pathways. Subsequently, bioassay-guided isolation was conducted during phytochemical investigation. Uric acid-induced HK-2 cells were then employed to validate the renal cytoprotective effects of the isolated compounds. Results Treatment with S. sessilifolia extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels by 65.15%, 47.95%, and 49.1%, respectively. Additionally, it decreased urinary protein excretion, and ameliorated renal injury and fibrosis in mice. The protective effects might be exerted by inhibiting the c-Myc/c-Fos/MAPK signaling pathway to maintain the homeostasis of renal tissue. Moreover, the bioactive compound stemoninine protected HK-2 cells against uric acid-induced oxidative stress, inflammatory response, proliferation, migration, and apoptosis. Conclusion The S. sessilifolia extract and its major bioactive compound, stemoninine, protected against hyperuricemic nephropathy by suppressing the c-Myc/c-Fos/MAPK signaling pathway.
研究领域:
民族药理学
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肾病学
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植物化学
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分子生物学
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信号转导
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2026
·Vol. 40
·期 14
·e72138
·
IF 4.3
Yong Sun,Huayue Wu,Yutong Zhou,Pengsheng Yin,Long Wu,Haiyang Li,Shi Zuo,Zhe Yang,Kun Cao
Liver fibrosis remains a major global health challenge, driving interest in bioactive metabolites from natural sources as potential therapies. Sodium butyrate (NaB), a gut microbiota–derived short‐chain fatty acid with notable anti‐fibrotic activity, shows promise, although its mechanisms remain unclear. This study aims to explore the molecular mechanisms through which NaB attenuates liver fibrosis. This study integrates bioinformatics and network pharmacology to predict the molecular targets through which NaB exerts its anti‐fibrotic effects. Candidate targets were validated through molecular docking, histopathology, CETSA, and SPR. The inferred mechanisms were further validated in vitro (LX‐2 cells) and in vivo (CCl 4 ‐induced mice) using Western blot, IF Co‐IP, RT‐qPCR, ELISA, and histopathological staining. HDAC3 was identified as a key driver of liver fibrosis. As a natural HDAC3 inhibitor, NaB markedly attenuated CCl 4 ‐induced hepatic injury and fibrosis, accompanied by reduced expression of HDAC3, c‐Myc, glycolytic enzymes (HK2, PFKFB3, and PKM2), and fibrotic markers (α‐SMA and type I collagen) in fibrotic liver tissues and LX‐2 cells. Mechanistically, NaB exerts its anti‐fibrotic effects by inhibiting HDAC3 expression and deacetylase activity, promoting c‐Myc acetylation and downregulating its expression, thereby suppressing glycolytic metabolic reprogramming in hepatic stellate cells. These findings indicate that NaB attenuates liver fibrosis by inhibiting HDAC3/c‐Myc–mediated metabolic reprogramming, revealing a gut‐derived anti‐fibrotic mechanism and potential therapeutic targets. This study explores the molecular mechanisms by which NaB ameliorates liver fibrosis from the perspectives of the gut–liver axis and metabolic reprogramming. In vivo and in vitro experiments demonstrate that gut‐derived NaB may alleviate liver injury and fibrosis by inhibiting hepatic stellate cell activation and aerobic glycolysis through the HDAC3/c‐Myc signaling axis.
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PubMed
高影响因子
MEDICAL ONCOLOGY
·
2025
·Vol. 42
·期 7
·1-12
·
IF 3.5
Tang Qing,Huang Kun,Li Mengjie,Zhao Ziqiao,Deng Yuanle,Zuo Yueqi,Wang Ningyu,Zhu Yongxia
Ovarian cancer is a deadly gynecological malignancy often diagnosed at an advanced stage, with few treatment options available. Polyphyllin I (PPI), the primary active ingredient of Paris polyphylla , has shown excellent anti-cancer activity against various cancers. However, studies on PPI use and ovarian cancer are limited, and the potential mechanisms remain unclear. This study explored the effects of anti-ovarian cancer and the potential mechanisms of action of PPI. Methods such as MTT, colony formation, three-dimensional spheroid formation, flow cytometry, and western blotting were employed to assess the anti-proliferative effects of PPI on different ovarian cancer cell lines. RNA sequencing was used to discover potential mechanisms by evaluating the effects of PPI on transcriptional signatures and identifying differences in gene expression patterns. The results indicate that PPI demonstrated dose- and time-dependent anti-proliferative effects on ovarian cancer cell lines. PPI also up-regulated 1518 genes and down-regulated 800 genes. The genes showed enrichment in the “apoptosis” gene sets, while exhibiting negative enrichment in the “cell cycle” and “Myc signaling pathway” gene sets. PPI caused cell cycle arrest at the G0/G1 phase by increasing the expression of p21 and p27 and inhibiting the activity of the CDK2/cyclin E complex. PPI triggered cell apoptosis, which was associated with elevated cellular reactive oxygen species and mitochondrial membrane potential depolarization. Finally, PPI reduced c-Myc protein levels and affected mRNA levels of c-Myc pathway-related genes. PPI effectively suppressed ovarian cancer cell proliferation, indicating its potential as a treatment option for ovarian cancer.
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PubMed
高影响因子
MOLECULES
·
2017
·Vol. 22
·期 11
·1814
·
IF 2.861
Wenrui Wang,Lingyu Zhang,Tiantian Chen,Wen Guo,Xunxia Bao,Dandan Wang,Baihui Ren,Haifeng Wang,Yu Li,Yueyue Wang,Sulian Chen,Baoding Tang,Qingling Yang,Changjie Chen
In this study, resveratrol-loaded solid lipid nanoparticles (Res-SLNs) were successfully designed to treat MDA-MB-231 cells. The Res-SLNs were prepared using emulsification and low-temperature solidification method. The Res-SLNs were spherical, with small size, negative charge, and narrow size distribution. Compared with free resveratrol, the Res-SLNs displayed a superior ability in inhibiting the proliferation of MDA-MB-231 cells. In addition, Res-SLNs exhibited much stronger inhibitory effects on the invasion and migration of MDA-MB-231 cells. Western blot analysis revealed that Res-SLNs could promote the ratio of Bax/Bcl-2 but decreased the expression of cyclinD1 and c-Myc. These results indicate that the Res-SLN may have great potential for breast cancer treatment.Keywords:solid lipid nanoparticle;resveratrol;breast cancer;cyclinD1
研究领域:
药理学
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肿瘤学
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纳米技术
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PubMed
高影响因子
TOXICOLOGY LETTERS
·
2021
·
IF 4.374
Shanqi Guo,Yangyi Zhang,Shuo Wang,Tong Yang,Baojie Ma,Xiaojiang Li,Yizhuo Zhang,Xingkang Jiang
Antimony is a common environmental contaminant that causes biological toxicity in exposed populations worldwide. Previous studies have revealed that antimony promotes prostate cancer growth by stabilizing the c-Myc protein and mimicking androgen activity. However, the role of lncRNAs in the regulation of antimony-induced carcinogenesis remains unknown, and the precise mechanisms need to be explored. In the present study, we found that chronic exposure to antimony promoted cell growth and lipid metabolic disequilibrium in prostate cancer. Mechanistically, we identified a long noncoding RNA molecule, PCA3, that was substantially upregulated in LNCaP cells in response to long-term antimony exposure. Functional studies indicated that abnormal PCA3 expression modulated antimony-induced proliferation and cellular triglyceride and cholesterol levels. In addition, PCA3 levels were found to be inversely correlated with MIR-132-3 P levels by acting as a decoy for MIR-132-3P. Besides, SREBP1 directly interacted with MIR-132-3 P to increase cell growth and disrupt lipid metabolism by targeting its 3’UTR regions. Taken together, our results revealed that lncRNA PCA3 promotes antimony-induced lipid metabolic disorder in prostate cancer by targeting MIR-132-3 P/SREBP1 signaling.
研究领域:
癌症生物学
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毒理学
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分子生物学
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环境健康
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 3
·期 1
·119-126
·
IF 0
Yinan Zhao,Shubiao Zhang,Yuan Zhang,Shaohui Cui,Huiying Chen,Defu Zhi,Yuhong Zhen,Shufen Zhang,Leaf Huang
Several novel tri-peptide cationic lipids were designed and synthesized for delivering DNA and siRNA. They have tri-lysine and tri-ornithine as headgroups, a carbamate group as a linker and 12 and 14 carbon atom alkyl groups as tails. These tri-peptide cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. Their particle size, zeta potential and DNA-binding were characterized to show that they were suitable for gene transfection. Further results indicate that these lipids can transfer DNA and siRNA very efficiently into NCI-H460 and Hep-2 tumor cells. The selected lipid, CDO14, was able to deliver combined siRNAs against c-Myc and VEGF for silencing distinct oncogenic pathways in lung tumors of mice, with little in vitro and in vivo toxicity.
研究领域:
药学
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分子生物学
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癌症研究
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DOI
PubMed
CANCER GENE THERAPY
·
2022
·Vol. 30
·期 2
·335-344
·
IF 5.854
Liu Jian,Mai Yumiao,Wang Yingjie,Chen Zhiwei,Wang Fei,Wei Huixia,Yao Qianghua
RAB3D, a small Ras-like GTPase involved in regulating secretory pathway, plays a cancer-promoting role in several solid tumors. However, its role in leukemogenesis remains unknown yet. Acute myeloid leukemia (AML) is a common acute leukemia with a high mortality. Here, we found the higher expression of RAB3D in bone marrow mononuclear cells derived from AML patients ( n = 54) versus healthy participants ( n = 20). The following loss- and gain-of-function experiments demonstrated that RAB3D promoted growth, enhanced colony formation and accelerated G1/S transition of U937, THP-1 and KG-1 AML cells. RAB3D silencing inhibited tumorigenesis of AML cells in vivo and delayed AML cells-induced death of mice. Interestingly, the expression of RAB3D is positively correlated with that of an oncogene mouse double minute 2 (MDM2) in bone marrow mononuclear cells of AML patients ( r = 0.923, p < 0.001). Intracellular MDM2 was conjugated with more ubiquitins and degraded faster when RAB3D was silenced. A commonly therapeutic target of AML, β-catenin signaling, was activated by RAB3D overexpression, but deactivated after MDM2 was silenced. The RAB3D-induced proliferation acceleration and β-catenin activation were abolished by MDM2 knockdown, implying that RAB3D function by stabilizing MDM2. In addition, c-MYC, a β-catenin downstream effector, was recruited directly to the RAB3D gene promoter (-360/-349 and -136/-125 sites) and induced its transcription. Collectively, this study demonstrates that RAB3D may exacerbate the malignant behaviors of AML cells through forming a positive feedback loop with MDM2/β-catenin/c-MYC signaling. RAB3D might be a novel target of clinical AML treatment.
研究领域:
肿瘤学
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血液学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
ZOOLOGICAL RESEARCH
·
2024
·Vol. 45
·期 6
·1287
·
IF 4
Yu-Tong Wu,Ze-Qiong Ru,Ying Peng,Zhe Fu,Qiu-Ye Jia,Zi-Jian Kang,Yuan-Sheng Li,Yu-Bing Huang,Sai-Ge Yin,Kun Guo,Nai-Xin Liu,Cheng-An Feng,Jing Tang,Bai-Yu Zhang,Zhi Yang,Ying Wang,Xin-Wang Yang
Individuals with diabetes frequently face serious challenges, including delayed wound healing and increased risk of infection. Notably, the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair, reducing the risk of infection, and enhancing overall skin health. Research has predominantly emphasized the re-epithelialization of diabetic wounds, with a paucity of in-depth studies on hair follicle regeneration. In the current study, we explored the effects of a bioactive amphibian-derived peptide, Cy RL-QN15 , on promoting hair regeneration in a diabetic skin model. In vivo experiments demonstrated that local treatment with Cy RL-QN15 not only accelerated wound healing of scalded skin on the backs of diabetic Kunming (KM) mice but also improved growth of damaged hair follicles. Additionally, back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy RL-QN15 treatment. Further analysis indicated that the hair-regenerating effects of Cy RL-QN15 were closely associated with the proliferation and migration of hair follicle stem cells (HFSCs). Cy RL-QN15 enhanced intracellular β-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs. The up-regulation in β-catenin modulated the levels of downstream proteins, such as c-MYC, Cyclin D1, and Lef1, ultimately inducing hair regeneration. This study not only reveals the robust effects of the bioactive peptide Cy RL-QN15 in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.
研究领域:
糖尿病研究
·
伤口愈合
·
干细胞生物学
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肽疗法
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分子生物学
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DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2024
·Vol. 30
·期 1
·1-16
·
IF 6
Xie Bin,Chen Qiong,Dai Ziyu,Jiang Chen,Chen Xi
Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression.Methods and resultsThe therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4’s protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions.Conclusion P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved.
研究领域:
呼吸病学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Anni Zhu,Zhiguang Duan,Yanru Chen,Chenhui Zhu,Daidi Fan
Background The aging of skeletal muscle is the leading cause of physical disability in older adults, currently effective treatment methods are lacking. Ginsenoside Rh4, an active component extracted from ginseng , possesses beneficial anti-inflammatory and anti-oxidative effects. Purpose The aim of this study was to elucidate the antioxidant effect of ginsenoside Rh4 on aging skeletal muscle and its molecular mechanism of anti-aging of skeletal muscle. Study design In this study, we employed a D-galactose-induced model of skeletal muscle aging to investigate whether ginsenoside Rh4 can delay the process of skeletal muscle senescence. Methods The effects of ginsenoside Rh4 on oxidative damage and inflammation in aging skeletal muscle were analyzed using immunofluorescence, immunohistochemistry , ELISA kits, H&E staining, flow cytometry, and protein immunoblotting . The changes of ginsenoside Rh4 on mitochondrial morphology were observed by transmission electron microscopy , and ELISA kits and protein immunoblotting analyzed the effects of ginsenoside Rh4 on mitochondrial homeostasis in skeletal muscle cells . The influence of ginsenoside Rh4 on the SIRT1 signaling pathway in aging skeletal muscle were investigated by protein immunoblotting, immunofluorescence, and β-galactosidase staining. Results Our results showed that Rh4 improved the morphology of muscle fibers and produced an anti-inflammatory response. Furthermore, in vitro experiments indicated that ginsenosides reduced the production of senescent cells, while Rh4 effectively alleviated oxidative damage in skeletal muscle and restored mitochondrial balance. Transcriptome analysis and molecular docking showed that Rh4 improved mitochondrial homeostasis and delayed skeletal muscle aging by regulating the PGC-1α-TFAM and HIF-1α-c-Myc pathways via targeting SIRT1. Conclusion Ginsenoside Rh4 improves oxidative stress and inflammation in skeletal muscle by activating SIRT1, deacetylating Nrf2, regulating PGC-1α-TFAM and HIF-1α-c-Myc pathways, and enhancing mitochondrial homeostasis, thus achieving the effect of delaying skeletal muscle aging.
研究领域:
药理学
·
老年学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2019
·Vol. 34
·期 4
·817-824
·
IF 3.766
Mingming Zhu,Xi Yu,Zongmei Zheng,Jiaming Huang,Xuepan Yang,Hongfei Shi
Cancer stem cells (CSCs) are considered as the origin and driving cells of cancer, and play a key role in the progress of cancer. Studies have shown that capsaicin exerted inhibitory effect on prostate cancer cells, however, the effects of capsaicin on prostate CSCs remain undefined. In the present study, we showed that capsaicin could downregulate prostate CSCs markers and inhibit the growth of PC-3 and DU145 prostate cancer stem cells. Further, we found capsaicin suppressed the expression of Wnt-2, p-GSK3β and β-catenin, along with downregulation of Wnt/β-catenin pathway target genes c-myc and cyclinD1. Using LiCl, a activator of Wnt/β-catenin pathway, we found activation of Wnt/β-catenin pathway could ameliorate the downregulation of prostate CSCs markers and the growth inhibition induced by capsaicin in prostate cancer stem cells. Those data suggested that the inhibition effect of capsaicin on prostate cancer stem cells and the anti-cancer effect of capsaicin on prostate cancer stem cell may be mediated by Wnt/β-catenin pathway. Findings from this study reveals for the first time the potential role and mechanisms of capsaicin on prostate cancer stem cells.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）