Z-Guggulsterone Induces Cell Cycle Arrest and Apoptosis by Targeting the p53/CCNB1/PLK1 Pathway in Triple-Negative Breast Cancer

Wu, Yihao; Zhou, Tao; Da, Qian; Liu, Xiaozhen; Xu, Yuhao; Hong, Weimin; Meng, Xuli; Tang, Hongchao

doi:10.1021/acsomega.2c07480

Cited by 7 publications

(6 citation statements)

References 41 publications

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“…This indicates the presence of significant differences in the specific compounds detected in each type of myrrh. For instance, the main components of Somali gum myrrh are trans-alpha-Bergamotene, beta-Bourbonene, Cyclohexane, and Germacrene D, while the main components of Somali natural myrrh are Naphthalene, 1,2,3,4,4a,5,6,8a-octahydro-4a,8-dimethyl-2-(1-methylethenyl)-, Cyclohexene and Germacrene D. The main components of grade A Kenyan natural myrrh are Cyclohexene and alfa-Copaene, while the main components of grade B Kenyan natural myrrh are Ethylene oxide and Cyclopenta [1,3]cyclopropa [1,2]benzene. The main components of grade A Kenyan vinegar-treated myrrh are Ethylene oxide and 1H-Cyclopenta [1,3]cyclopropa [1,2]benzene, while the main components of grade B Kenyan vinegar-treated myrrh are (1R)-2,6,6-Trimethylbicyclo[3.1.1]hept-2-ene and 2-methyl-5-(1-methylethyl)-.…”

Section: Gc-ms Analysis Results Of Myrrh Volatile Gasesmentioning

confidence: 99%

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Improved Recognition Accuracy of Myrrh Decoction Pieces by Electronic Nose Technology Using GC-MS Analysis and Sensor Selection

Zhou

Xie

et al. 2023

Chemosensors

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The quality of myrrh decoction pieces can be influenced by factors such as origin, source, and processing methods. The quality of myrrh in the market varies greatly, and adulteration is a serious issue, highlighting the urgent need for improved quality control measures. This study explores the integration of GC–MS analysis and sensor selection in electronic nose technology for the improved classification of myrrh decoction pieces. GC–MS analysis revealed the presence of 130 volatile compounds in the six myrrh samples, primarily composed of alkene compounds, and each sample exhibited variations in composition. An electronic nose system was designed using a sensor array consisting of six sensors selected from twelve sensors capable of detecting volatile compounds consistent with myrrh composition, including WO3 quantum dots, Fe2O3 hollow nanorods, ZnFe2O4 nanorods, SnO2 nanowires, and two commercially available sensors. The sensors exhibited distinct response patterns to the myrrh samples, indicating their suitability for myrrh analysis. Various sensor parameters, including response, response and recovery time, integral area, and slope, were computed to characterize the sensors’ performance. These parameters provided valuable insight into the sensor–gas interactions and the unique chemical profiles of the myrrh samples. The LDA model demonstrated high accuracy in differentiating between the myrrh types, utilizing the discriminative features captured by the sensor array, with a classification accuracy of 90% on the testing set. This research provides a comprehensive evaluation method for the quality control of myrrh pieces and a scientific basis for the development and utilization of myrrh.

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Section: Gc-ms Analysis Results Of Myrrh Volatile Gasesmentioning

confidence: 99%

“…Myrrh is the dry resin from Commiphora myrrha Engl. or Commiphora molmol Engl, which grows in arid regions of the Middle East, Africa, and Asia [1]. Myrrh has been widely used in traditional medicine for thousands of years for its anti-inflammatory, analgesic, antimicrobial, and antioxidant properties [2,3].…”

Section: Introductionmentioning

confidence: 99%

Improved Recognition Accuracy of Myrrh Decoction Pieces by Electronic Nose Technology Using GC-MS Analysis and Sensor Selection

Zhou

Xie

et al. 2023

Chemosensors

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“…30 Previous studies have indicated that p53 down-regulated the expression of CCNB1, and CCNB1 silencing inhibits cell proliferation and induces cell senescence via activation of the p53 signaling pathway. 31,32 The expression of CCNB1 was elevated in various cancers, and the high expression of CCNB1 was related to poor prognosis. 32,33 Recent research has also revealed that the expression of CCNB1 increased in human thoracic aortic dissection and the genetic variants in CCNB1 correlated with the risk of coronary in-stent restenosis.…”

Section: Discussionmentioning

confidence: 99%

“…Cyclin B1 (CCNB1) is a key factor in the initiation of mitosis, and CCNB1 can form complexes with CCNB2 and CDK1, thus regulating the G2/M phases of mammalian cell 30 . Previous studies have indicated that p53 down‐regulated the expression of CCNB1, and CCNB1 silencing inhibits cell proliferation and induces cell senescence via activation of the p53 signaling pathway 31,32 . The expression of CCNB1 was elevated in various cancers, and the high expression of CCNB1 was related to poor prognosis 32,33 .…”

Section: Discussionmentioning

confidence: 99%

Kielin/chordin‐like protein deficiency aggravates pressure overload‐induced cardiac dysfunction and remodeling via P53/P21/CCNB1 signaling in mice

Xu,

Zheng,

Pan

et al. 2024

The FASEB Journal

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Targeting cardiac remodeling is regarded as a key therapeutic strategy for heart failure. Kielin/chordin‐like protein (KCP) is a secretory protein with 18 cysteine‐rich domains and associated with kidney and liver fibrosis. However, the relationship between KCP and cardiac remodeling remains unclear. Here, we aimed to investigate the role of KCP in cardiac remodeling induced by pressure overload and explore its potential mechanisms. Left ventricular (LV) KCP expression was measured with real‐time quantitative PCR, western blotting, and immunofluorescence staining in pressure overload‐induced cardiac remodeling in mice. Cardiac function and remodeling were evaluated in wide‐type (WT) mice and KCP knockout (KO) mice by echocardiography, which were further confirmed by histological analysis with hematoxylin and eosin and Masson staining. RNA sequence was performed with LV tissue from WT and KO mice to identify differentially expressed genes and related signaling pathways. Primary cardiac fibroblasts (CFs) were used to validate the regulatory role and potential mechanisms of KCP during fibrosis. KCP was down‐regulated in the progression of cardiac remodeling induced by pressure overload, and was mainly expressed in fibroblasts. KCP deficiency significantly aggravated pressure overload‐induced cardiac dysfunction and remodeling. RNA sequence revealed that the role of KCP deficiency in cardiac remodeling was associated with cell division, cell cycle, and P53 signaling pathway, while cyclin B1 (CCNB1) was the most significantly up‐regulated gene. Further investigation in vivo and in vitro suggested that KCP deficiency promoted the proliferation of CFs via P53/P21/CCNB1 pathway. Taken together, these results suggested that KCP deficiency aggravates cardiac dysfunction and remodeling induced by pressure overload via P53/P21/CCNB1 signaling in mice.

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“…The Cell Counting Kit-8 (CCK-8) (Topscience, Shanghai, China) was employed for determination of the muscone-based regulation of cell survivability. Approximately 4 × 10 3 cells were introduced to individual wells of 96-well plates, and plates underwent a 24 h-incubation at 37 °C and 5% CO 2 humid chamber [ 19 – 21 ]. Cells were exposed to several muscone concentrations followed by 24, 48, or 72 h incubation.…”

Section: Methodsmentioning

confidence: 99%

Muscone abrogates breast cancer progression through tumor angiogenic suppression via VEGF/PI3K/Akt/MAPK signaling pathways

Wang,

Liu,

Hong

et al. 2024

Cancer Cell Int

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Background Angiogenesis strongly reflects poor breast cancer outcome and an important contributor to breast cancer (BC) metastasis; therefore, anti-angiogenic intervention is a potential tool for cancer treatment. However, currently used antibodies against vascular endothelial growth factor A (VEGFA) or inhibitors that target the VEGFA receptor are not effective due to weak penetration and low efficiency. Herein, we assessed the anti-BC angiogenic role of muscone, a natural bioactive musk constituent, and explored possible anti-cancer mechanisms of this compound. Methods CCK-8, EdU, scratch and Transwell assessments were employed to detect the muscone-mediated regulation of breast cancer (BC) and human umbilical vein endothelial cells (HUVECs) proliferation and migration. Tube formation, matrigel plug assay and zebrafish assay were employed for assessment of regulation of tumor angiogenesis by muscone. In vivo xenograft mouse model was constructed to compare microvessel density (MVD), vascular leakage, vascular maturation and function in muscone-treated or untreated mice. RNA sequencing was performed for gene screening, and Western blot verified the effect of the VEGFA-VEGFR2 pathway on BC angiogenic inhibition by muscone. Results Based on our findings, muscone suppressed BC progression via tumor angiogenic inhibition in cellular and animal models. Functionally, muscone inhibited BC cell proliferation and migration as well as tumor cell-conditioned medium-based endothelial cell proliferation and migration. Muscone exhibited a strong suppressive influence on tumor vasculature in cellular and animal models. It abrogated tumor cell growth in a xenograft BC mouse model and minimized tumor microvessel density and hypoxia, and increased vascular wall cell coverage and perfusion. Regarding the mechanism of action, we found that muscone suppressed phosphorylation of members of the VEGF/PI3K/Akt/MAPK axis, and it worked synergistically with a VEGFR2 inhibitor, an Akt inhibitor, and a MAPK inhibitor to further inhibit tube formation. Conclusion Overall, our results demonstrate that muscone may proficiently suppress tumor angiogenesis via modulation of the VEGF/PI3K/Akt/MAPK axis, facilitating its candidacy as a natural small molecule drug for BC treatment.

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Z-Guggulsterone Induces Cell Cycle Arrest and Apoptosis by Targeting the p53/CCNB1/PLK1 Pathway in Triple-Negative Breast Cancer

Cited by 7 publications

References 41 publications

Improved Recognition Accuracy of Myrrh Decoction Pieces by Electronic Nose Technology Using GC-MS Analysis and Sensor Selection

Improved Recognition Accuracy of Myrrh Decoction Pieces by Electronic Nose Technology Using GC-MS Analysis and Sensor Selection

Kielin/chordin‐like protein deficiency aggravates pressure overload‐induced cardiac dysfunction and remodeling via P53/P21/CCNB1 signaling in mice

Muscone abrogates breast cancer progression through tumor angiogenic suppression via VEGF/PI3K/Akt/MAPK signaling pathways

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