scholarly journals Ethyl Acetate Fraction from Hedyotis diffusa plus Scutellaria barbata Suppresses Migration of Bone-Metastatic Breast Cancer Cells via OPN-FAK/ERK/NF-κB Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Ting Fang ◽  
Ying-Xuan Yan ◽  
Yue Yang ◽  
Ya-Xin Lv ◽  
Qing-Qi Chang ◽  
...  

Hedyotis diffusa plus Scutellaria barbata is a couplet of medicinal that has been commonly used to treat inflammation-related diseases and various types of tumors. However, the effect of this couplet on tumor cell migration has not been elucidated. With the aid of MCF-7-BOM, a bone-metastatic subline of ER + breast cancer MCF-7, we showed that ethyl acetate fraction extracted at an equal weight ratio of Hedyotis diffusa plus Scutellaria barbata (EA11) inhibited cell migration of MCF-7-BOM in a concentration-dependent manner. To define the underlying molecular mechanism, we revealed that EA11 reduced the expression of osteopontin (OPN) and interfered with the FAK/ERK/NF-κB signaling pathways, which are both critical for breast cancer bone metastasis. This study strongly suggested EA11 may represent a potential therapeutic agent against bone metastasis of breast cancer.

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yuan Xu ◽  
Xiao-Xia Chen ◽  
Yi-Xin Jiang ◽  
Dan-Dan Zhang

Hedyotis diffusa Willd and Scutellaria barbata D. Don (HDSB) were the core couplet in medicines that were commonly used for the purpose of anti-inflammation and anticancer treatments in China. However, biological properties of this couplet have not been fully elucidated. In this study, we screened fractions of HDSB for their anti-inflammatory activities and explored pertinent molecular mechanisms on murine macrophage RAW264.7 cell model. Ethyl acetate fraction from the aqueous extract of the couplet at equal weight ratio (EA11) showed the strongest inhibition of the nitrite accumulation in supernatant of RAW264.7 cells stimulated with lipopolysaccharide (LPS)/interferon-γ (IFN-γ). In addition, EA11 inhibited iNOS and IL-1β expression in a concentration-dependent manner while promoting the expression of HO-1 and PPAR-γ. Anti-inflammatory capability is most likely facilitated by its inhibitory effect on JNK signaling pathway and miR-155 expression. This study suggests that EA11 may be represented as a potential anti-inflammatory therapeutic candidate.


Author(s):  
Nunuk Aries Nurulita ◽  
Edy Meiyanto ◽  
Sugiyanto Sugiyanto

Gynura procumbens is widely used as traditional remedy in South-East Asia. Gynura procumbens exhibites anti inflammatory, antioxidant, and reduced blood pressure activity. The aim of this study was to determine chromatographic profile of ethyl acetate fraction of Gynura procumbens (FEG) and to investigate its cytotoxic properties and selectivity to colon cancerand breast cancer cancer cells. The chromatographic profile of FEG was determined using HPTLC densitometric and HPLC. MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine the growth inhibitory effect of FEG on the growth of WiDr, MCF-7, and T47D cells. NIH3T3, a normal cells was used to determine the selectivity of FEG, which contained small amount of quercetin as identified from chromatographic profile both HPTLC and HPLC. FEG inhibited cell growth of WiDr, of MCF-7 and of T47D cells in time dependent manner. Quercetin affected cell growth inhibition approximately two fold higher at WiDr and MCF-7, whereas FEG had lower effect on T47D cell. Quercetin did not seem as the main active compound of FEG. At this study, FEG caused less inhibition on the growth of NIH3T3 cells than that of on all cell lines. Selectivity index (SI) of FEG on WiDr, MCF-7 and T47D were 4.97, 2.77 and 7.79 respectively. According to the datas obtained, FEG possesses moderate to high cytotoxicity properties on WiDr, MCF-7 and T47D cells. FEG demonstrates selective effect against cancer cells and reveals prospective properties as cancer chemoprevention agent.Keywords: Gynura procumbens, colon cancer, breast cancer, cytotoxicity, selectivity


Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4293
Author(s):  
Xiaowen Liu ◽  
Manuel A. Riquelme ◽  
Yi Tian ◽  
Dezhi Zhao ◽  
Francisca M. Acosta ◽  
...  

ATP released by bone osteocytes is shown to activate purinergic signaling and inhibit the metastasis of breast cancer cells into the bone. However, the underlying molecular mechanism is not well understood. Here, we demonstrate the important roles of the CXCR4 and P2Y11 purinergic receptors in mediating the inhibitory effect of ATP on breast cancer cell migration and bone metastasis. Wound-healing and transwell migration assays showed that non-hydrolysable ATP analogue, ATPγS, inhibited migration of bone-tropic human breast cancer cells in a dose-dependent manner. BzATP, an agonist for P2X7 and an inducer for P2Y11 internalization, had a similar dose-dependent inhibition on cell migration. Both ATPγS and BzATP suppressed the expression of CXCR4, a chemokine receptor known to promote breast cancer bone metastasis, and knocking down CXCR4 expression by siRNA attenuated the inhibitory effect of ATPγS on cancer cell migration. While a P2X7 antagonist A804598 had no effect on the impact of ATPγS on cell migration, antagonizing P2Y11 by NF157 ablated the effect of ATPγS. Moreover, the reduction in P2Y11 expression by siRNA decreased cancer cell migration and abolished the impact of ATPγS on cell migration and CXCR4 expression. Similar to the effect of ATPγS on cell migration, antagonizing P2Y11 inhibited bone-tropic breast cancer cell migration in a dose-dependent manner. An in vivo study using an intratibial bone metastatic model showed that ATPγS inhibited breast cancer growth in the bone. Taken together, these results suggest that ATP inhibits bone-tropic breast cancer cells by down-regulating the P2Y11 purinergic receptor and the down-regulation of CXCR4 expression.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yue Yang ◽  
Ting Fang ◽  
Yi-Lan Cao ◽  
Ya-Xin Lv ◽  
Qing-Qi Chang ◽  
...  

Background. Hedyotis diffusa (HD) Willd. and Scutellaria barbata (SB) D. Don in different ratios have been frequently used to treat various cancers in clinical Traditional Chinese Medicine prescriptions. However, the optimal ratio, active fraction, and molecular mechanisms associated with the anti-breast cancer role of this herbal couplet have not been elaborated. Methods. To screen out the optimal ratio of this herbal couplet, we compare aqueous extracts of HD, SB, or HD plus SB in different weight ratios (HS11, HS12, HS21) for their anticancer effects on murine breast cancer 4T1 cells in vitro and in vivo. EA11, the ethyl acetate fraction from HS11 (the aqueous extract of the couplet at an equal weight ratio), is further assessed for its antiproliferative effect as well as the antitumorigenic impact with the aid of immunocompetent mice. Colony formation, flow cytometry, western blot, ELISA, and qRT-PCR are used to elucidate mechanisms underlying EA11-led effects. Results. HS11 presents the most potential suppression of 4T1 cell proliferation and tumor growth among these aqueous extracts. The comparison results show that EA11 is more effective than HS11 in vitro and in vivo. EA11 inhibits colony formation and induces apoptosis in a concentration-dependent manner. EA11 reduces the protein expressions of PDE7B, PD-L1, β-catenin, and cyclin D1 while elevating the concentration of cellular cAMP and miR-200c expression in 4T1 cells. Additionally, EA11 exerts its anticancer effect partially via the inactivation of MAPK and AKT signaling pathways. Conclusions. This study implicates that EA11 prevents breast tumor development by interfering with the miR-200c-PDE7B/PD-L1-AKT/MAPK axis. EA11 may represent a potential therapeutic candidate for breast cancer.


Author(s):  
Riris Istighfari Jenie ◽  
Sri Handayani ◽  
Ratna Asmah Susidarti ◽  
Zalinar Udin ◽  
Edy Meiyanto

Overexpression of HER2 in breast cancer cell is found on invasive breast cancer and correlated with worse prognosis. Caesalpinia sappan L shows cytotoxic activity on various cancer cells. The goal of this research is to determine the cytotoxic activity and inhibition of migration and invasion of ethyl acetate fraction of Caesalpinia sappan L. (FEA) on HER2 overexpression-breast cancer cells (MCF-7/HER2). The MTT and flow cytometry assay showed that FEA revealed cytotoxic effect in a dose-dependent manner (IC50= 34 ± 3.1 µg/ml) and induced apoptosis, S and G2/M phase accumulation. Wound healing assay, gelatin zymography and immunoblotting assay showed that FEA inhibited migration and suppressed MMP2, MMP9, HER2 and Rac1 protein level. Thus, ethyl acetate fraction of Caesalpinia sappan L. is potential to be developed on future research especially to treat metastatic breast cancer with HER2 overexpression.Keywords: Ethyl acetate fraction of Caesalpinia sappan L, cytotoxic effect, migration and invasion, MCF-7/HER2 cells


2021 ◽  
Vol 901 ◽  
pp. 16-21
Author(s):  
Supavadee Boontha ◽  
Benjaporn Buranrat ◽  
Prapapan Temkitthawon ◽  
Tasana Pitaksuteepong

Phlogacanthus pulcherrimus T. Anderson (PPT) is an edible plant found in the northern and northeastern regions of Thailand. There is limited information about the anti-breast cancer activity of the ethanolic leaf extract of PPT. This study aimed to evaluate the effects of an ethanolic leaf extract of PPT on MCF-7 breast cancer cell lines. The biological effects, including cytotoxicity, cell apoptosis, colony formation, reactive oxygen species (ROS) formation and cell migration, were determined by a means of sulforhodamine B (SRB), acridine orange/ethidium bromide (AO/EB) staining, a clonogenic assay, flow cytometry and a scratch wound healing assay, respectively. The results demonstrated that the PPT extract showed cytotoxic on MCF-7 cells in a dose-dependent manner with 50% inhibitory concentration (IC50) values of 119.9 ± 12.1 and 51.3 ± 4.7 μg/mL at 24 h and 48 h incubation, respectively. In addition, the extract exhibited cell apoptosis in a dose-dependent manner when used at a concentration of 50–100 μg/mL and inhibited colony formation with an IC50 value of 26.0 ± 2.0 μg/mL when compared with the control group. The extract induced ROS formation in a dose-dependent manner when used at a concentration of 50–100 μg/mL. The extract suppressed MCF-7 cell migration, with significant effect at 25 μg/mL. These results indicate that PPT ethanolic leaf extract has an anticancer activity against MCF-7 breast cancer cells and may be useful for prevention and treatment of breast cancer.


2018 ◽  
Vol 11 (13) ◽  
pp. 194
Author(s):  
Urip Harahap ◽  
Poppy Anjelisa Zaitun Hasibuan ◽  
Panal Sitorus ◽  
Denny Satria

 Objective: This study was carried out to investigate the cytotoxic activity toward 4T1 and MCF-7 cell lines of Picria fel-terrae Lour. herb fractions.Methods: P. fel-terrae Lour. herb powder was extracted by maceration method with n-hexane, ethyl acetate, and ethanol solvent. In vitro study was using MTT method toward 4T1 and MCF-7 cell lines.Results: The inhibitory concentration 50% was 234.10 ± 7.85, 50.49 ± 1.07, and 212.53 ± 7.55 μg/mL for 4T1 and 84.62 ± 1.44, 56.79 ± 0.22, and 235.51 ± 4.77 μg/mL for MCF-7 cell lines, respectively.Conclusion: The results reveal that P. fel-terrae Lour. herb fractions provide effective as anticancer. Our further study is to assess the mechanism of ethyl acetate fraction in inhibit angiogenesis and metastatic in breast cancer.


2019 ◽  
Vol 16 (2) ◽  
pp. 73-82
Author(s):  
Adhe Retnantya Pamungkas ◽  
Peni Indrayudha

Bitter melon is one of fruit that have pharmacological effects such as an anticancer which potentially active on breast cancer cell MCF-7. The aim of this study was to compare the potential cytotoxic activity between ethanol extract of pare and the results of ethanol, ethyl acetate and n-hexane fraction on MCF-7 breast cancer cells and to determine the class of compounds contained in each sample. Pare’s powder was extracted with maceration method in 80% ethanol solvent and then continue to fractionated in 96% ethanol, ethyl acetate and hexane solvent. Extract and fractions were continue to cytotoxic assay using the MTT assay method. Cytotoxic test results showed that the ethanolic extract had no potential cytotoxic activity. Ethyl acetate fraction with the highest concentration 16 µg/mL has the highest potential inhibition 43,87% on MCF-7 cells population. Extract and fractions than continue to phytochemical screening with Thin Layer Chromatography (TLC) method. TLC detection showed that n-hexane fraction contained more compound groups than ethanolic extract, ethanolic-water fraction and ethyl acetate fraction.


2018 ◽  
Vol 18 (4) ◽  
pp. 573-582 ◽  
Author(s):  
Khaled R.A. Abdellatif ◽  
Mostafa M. Elbadawi ◽  
Mohammed T. Elsaady ◽  
Amer A. Abd El-Hafeez ◽  
Takashi Fujimura ◽  
...  

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.


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