Journal of Cancer
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2022
·
IF 4.478
Shixin Chan,Rui Sun,Xucan Tu,Manyu Guo,Qianqian Yuan,Zhen Yu,Zhenglin Wang,Shaocheng Hong,Wei Han,Bingbing Zou,Zeng Li,Huabing Zhang,Wei Chen
Colorectal cancer (CRC) is a malignant disease that is a serious threat to human health. Rutaecarpine (RUT) is an important bioactive alkaloid of Evodia rutaecarpa. According to previous studies, RUT suppressed the proliferation of several human tumors. However, its role in colorectal tumorigenesis remained unknown. The aim of the present study was to determine the functions of RUT in CRC. Here, we have demonstrated that RUT inhibited the proliferation, migration and invasion of CRC cells in vitro . Further, RUT was found to induce the apoptosis of CRC cells. Mechanistically, RUT decreased the phosphorylation levels of NF-κB and STAT3. Moreover, treatment with RUT upregulated the expression of cleaved-Caspase3 and downregulated the expression of Bcl-2 in CRC. In addition, our findings suggested that RUT inhibited the growth and lung metastasis of CRC Cells in vivo . Based on immunofluorescence analysis, the expression of Ki67 was downregulated while that of cleaved-Caspase3 was upregulated in RUT-treated tumors compared with control-treated tumors. Taken together, our findings indicate that RUT can inhibit the proliferation and migration of CRC cells, and induce the apoptosis of CRC cells by inactivating NF-κB/STAT3 signaling. Our study highlights the potential clinical application of RUT for the treatment of CRC.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
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2017
·Vol. 7
·期 86
·54369-54378
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IF 3.108
Mengqiao Lian,Yuchao Sun,Yuan Lin,Jin Wen,Marwan Almoiliqy,Bin Xu,Yanli Li,Ming Xu,Dapeng Chen,Zeyao Tang,Li Wang
Catalpol, an iridoid glucoside isolated from the radix of Rehmannia glutinosa Libosch, is found to have a wide variety of biological activities. Based on our pre-experiments, we proposed that catalpol pretreatment could protect against intestinal ischemia/reperfusion (I/R) injury and the JAK2/STAT3 signaling pathway might play an important role in the protection. Both in vivo intestinal I/R-injured rats and in vitro hypoxia/reoxygenation (H/R)-injured IEC-6 cells were used in the present study. The results confirmed our proposal. The in vivo results showed that catalpol (25, 50 mg kg−1) significantly attenuated rat intestinal I/R injury by decreasing pro-inflammatory cytokines, reducing oxidative stress, and restoring intestinal barrier function without affecting the corresponding controls. Catalpol pretreatment significantly increased the Bcl-2/Bax ratio, and decreased cleaved caspase3, p-JAK2, and p-STAT3 protein expression without affecting total JAK2 and STAT3 in vivo and in vitro, showing that catalpol inhibited apoptosis through selectively inhibiting p-JAK2 and p-STAT3. In vitro studies indicated that catalpol (40 μM) pretreatment significantly and selectively inhibited p-STAT3 nuclear translocation and transfection of JAK2 siRNA significantly decreased JAK2, p-JAK2, STAT3, p-STAT3, and other apoptosis-related proteins in H/R-injured IEC-6 cells, suggesting that JAK2 siRNA partially simulated the effects of catalpol on apoptosis-related proteins. JAK2 siRNA + catalpol could not further decrease JAK2, p-JAK2, STAT3, p-STAT3, and other apoptosis-related proteins, suggesting that inhibition of the JAK2/STAT3 signaling pathway plays a key role in catalpol-induced protective effects. Our results suggest that p-JAK2 is the key target in catalpol-induced protection against intestinal I/R injury, providing information for further translational studies.
研究领域:
药理学
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病理生理学
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分子生物学
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产品关联
DOI
高影响因子
Marine Drugs
·
2024
·Vol. 22
·期 6
·250
·
IF 4.9
Wanting Hao,Leyan Wang,Tongqiang Xu,Geng Jia,Yuqi Jiang,Chong Qin,Xiaoyang Li
Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence rate. Current research has demonstrated that class I HDAC inhibitors can downregulate anti-apoptotic proteins, leading to apoptosis of AML cells. In the present investigation, we conducted structural modifications of marine cytotoxin Santacruzamate A (SCA), a compound known for its inhibitory activity towards HDACs, resulting in the development of a novel series of potent class I HDACs hydrazide inhibitors. Representative hydrazide-based compound25cexhibited concentration-dependent induction of apoptosis in AML cells as a single agent. Moreover,25cexhibited a synergistic anti-AML effect when combined with Venetoclax, a clinical Bcl-2 inhibitor employed in AML therapy. This combination resulted in a more pronounced downregulation of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with a significant upregulation of the pro-apoptotic protein cleaved-caspase3 and the DNA double-strand break biomarker γ-H2AX compared to monotherapy. These results highlighted the potential of25cas a promising lead compound for AML treatment, particularly when used in combination with Venetoclax.
研究领域:
肿瘤学
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药理学
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血液学
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DOI
高影响因子
INTERNATIONAL UROLOGY AND NEPHROLOGY
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2023
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IF 2
Wang Zhi-shun,Shu Bo,Han Qi,Li Guo-hao,Guo Yong-lian
Purpose To investigate the effect of grape seed-derived proanthocyanidin B2 (GSPB2) pretreatment on acute renal ischemia–reperfusion injury model of mice. Methods 50 mice were divided into 5 groups: Sham group: mice were treated with right nephrectomy. GSPB2 group: GSPB2 was injected intraperitoneally 45 min before right nephrectomy. IRI group: right kidney was resected and the left renal arteriovenous vessel was blocked for 45 min. GSPB2 + IRI group: GSPB2 was intraperitoneally injected 45 min before IRI established. GSPB2 + BRU + IRI group: GSPB2 and brusatol (BRU) were injected intraperitoneally 45 min before IRI established. Creatinine and urea nitrogen of mice were detected, and the kidney morphology and pathological changes of each group were detected by HE staining, PAS staining and transmission electron microscopy. Expressions of Nrf2, HO-1, GRP78, CHOP, and cleaved-caspase3 were detected by immunofluorescence staining and western blotting. Results Morphology and mitochondrial damages of kidney in GSPB2 + IRI group were significantly alleviated than those in IRI group. Expression levels of Nrf2 and HO-1 were significantly higher in GSPB2 + IRI group than those in IRI group. Expression levels of GRP78, CHOP and cleaved-caspase3 were significantly lower in GSPB2 + IRI group than those in IRI group. However, compared to GSPB2 + IRI group, protective effects of GSPB2 pretreatment were weakened in GSPB2 + BRU + IRI group. Conclusions GSPB2 pretreatment could alleviate oxidative stress damage and reduce apoptosis of renal tubular epithelial cells, which might be related to activating the antioxidant system, up-regulating the expression of Nrf2 and HO-1, inhibiting the expressions of GRP78, CHOP and cleaved-caspase3. However, the protective effect could be reversed by brusatol.
研究领域:
药理学
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肾脏生理学
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分子生物学
·
病理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Haiting Liu,Guangqing Cai,Shuai Yuan,Xionghui Zhou,Rong Gui,Rong Huang
Triple-negative breast cancer (TNBC) is characterized by high malignancy and limited treatment options. Given the pressing need for more effective treatments for TNBC, this study aimed to develop platelet membrane (PM)-camouflaged silver metal–organic framework nanoparticles (PM@MOF-Ag NPs), a biomimetic nanodrug. PM@MOF-Ag NP construction involved the utilization of 2-methylimidazole and silver nitrate to prepare silver metal–organic framework (MOF-Ag) NPs. The PM@MOF-Ag NPs, due to their camouflage, possess excellent blood compatibility, immune escape ability, and a strong affinity for 4T1 tumor cells. This enhances their circulation time in vivo and promotes the aggregation of PM@MOF-Ag NPs at the 4T1 tumor site. Importantly, PM@MOF-Ag NPs demonstrated promising antitumor activity in vitro and in vivo. We further revealed that PM@MOF-Ag NPs induced tumor cell death by overproducing reactive oxygen species and promoting cell apoptosis. Moreover, PM@MOF-Ag NPs enhanced apoptosis by upregulating the ratios of Bax/Bcl-2 and cleaved caspase3/pro-caspase3. Notably, PM@MOF-Ag NPs exhibited no significant organ toxicity, whereas the administration of MOF-Ag NPs resulted in liver inflammation compared to the control group.
研究领域:
肿瘤学
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纳米技术
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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