Adenosine A1 Receptor Antagonist Up-regulates Casp3 and Stimulates Apoptosis Rate in Breast Cancer Cell Line T47D

2020 ◽  
Vol 9 (1) ◽  
pp. 14-20
Author(s):  
Mohammad Zamani Rarani ◽  
Fahimeh Zamani Rarani ◽  
Ali Valiani ◽  
Zeinolabedin Shrifian Dastjerdi ◽  
Elias Kargar Abargouei ◽  
...  

Background: Adenosine receptor family, especially A1 type is-overexpressed in breast-derived tumor cells and the P53 gene is mutant in some of these cells while the casps gene is of wild type as well. The aim of this study was to evaluate the effect of the A1 receptor function on cell programmed death or proliferation, as well as the relationship between this receptor stimulation/inhibition and caspase 3 (casp3) expression in T47D cell line that has a mutant and non-functional P53 gene. Materials and Methods: The expression of casps3 was measured by real-time polymerase chain reaction and then flow cytometery and MTT assay were used to assess the apoptotic and proliferation cell rate after the treatment of T47D cells with specific agonist N6-cyclopentyladenosine (CPA) and antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) of this receptor 24, 48, and 72 hours after treatment. Result: Our results indicated that DPCPX significantly induces apoptosis in T47D cells and the rate of survival cell after the reduction of this treatment, especially 72 hours after treatment. Finally, the expression of casp3 was up-regulated by DPCPX treatment, especially in 72 hours while CPA treatment had opposite results (P>0.05). Conclusion: In general, DPCPX could up-regulate casp3 gene expression and subsequently increase the apoptosis rate in T47D cells with casp3 expression without the P53 gene interference. Therefore, adenosine A1 receptor antagonists may be introduced as anti-cancer agents.

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 168
Author(s):  
Woro Anindito Sri Tunjung ◽  
Puspa Restu Sayekti

Background: Breast cancer is the second leading cause of death in women. Alternative medicine with high efficacy is needed for breast cancer treatments, for example induction of apoptosis using natural products. It has been found that many natural apoptosis-inducing compounds are isolated from marine sponge. The objective of this study is to analyze the ability of extracts of the sponge Ancorina sp. to induce apoptosis on human breast cancer T47D cell line and find out its mechanism. Methods: T47D cells were treated with crude extracts of methanol, dichloromethane:methanol (1:1) and dichloromethane Ancorina sp. for 24 h, and doxorubicin was used as a positive control. Methods used for this study were MTT assay to examine cell viability and determine IC50 of the three extracts, while the percentage of apoptosis and caspase-3 were investigated by flow cytometry. Results: IC50 values of methanol, dichloromethane:methanol (1:1), and dichloromethane extract were 84.25, 121.45, and 99.85μg/mL respectively. The percentages of apoptotic cells after treatment with methanol, dichloromethane:methanol (1:1), and dichloromethane extracts were 88.68, 27.54 and 53.63% respectively, whereas the percentage of caspase-3 was 77.87, 12.66 and 12.97%, respectively. Conclusions: These results revealed that all extracts of Ancorina sp. have strong or moderate cytotoxicity and have the ability to induce apoptosis on T47D human breast cancer cell line. However, methanol crude extract has high efficacy to induce apoptosis through caspase-3 activation compared to the other extracts. Hence methanol extract warrants further investigation as a natural medicine for human breast cancer.


2016 ◽  
Vol 116 (04) ◽  
pp. 242-246 ◽  
Author(s):  
M. Nikbakht Dastjerdi ◽  
A. Valiani ◽  
M. Mardani ◽  
M. Zamani Ra

Author(s):  
Rina Andriyani ◽  
Chandra Risdian ◽  
Zalinar Udin

Drug discovery for cancer medication is the most important effort that researcher do at this time. Indonesia bio diversities have possibility as a cancer medicine sources. Finding a herbal medicine for cancer treatment is a first step to find a right cancer medicine in the future. This research has already completed for the earlier another research. Some fractions of Hedyotis corymbosa extract has been analyzed using Sulforhodamine B method with UV wavelength 515 nm against T47D cell line, a human breast cancer. There are Hexane extract, Methylene chloride extract and Ethyl acetate extract, and give inhibitory concentration 50 (IC50)  of 33.45 µg/ml, 54.59 µg/ml and 52.58 µg/ml, respectively. Ethanolic extract, itself has IC50 of 61.57 µg/ml, whereas IC50 value of Cisplatinum is  9.63 µg/ml. There is a difference between the ethanolic extracts with the other fraction.Keywords: breast cancer, herbal medicine, T47D, Hedyotis corymbosa


2018 ◽  
Vol 18 (1) ◽  
pp. 102 ◽  
Author(s):  
Chairil Anwar ◽  
Yogo Dwi Prasetyo ◽  
Sabirin Matsjeh ◽  
Winarto Haryadi ◽  
Eti Nurwening Sholikhah ◽  
...  

The synthesis of chalcone derivatives as target compounds and anticancer test against breast (T47D) and colon (WiDr) cell line had been performed. The synthesis was performed by Claisen-Schmidt condensation by using acetophenone and benzaldehyde derivatives. The anticancer activity test of chalcone derivatives was carried out by MTT assay against T47D and WiDr cell lines. The synthesis was started by reacting 4-hydroxyacetophenone and benzaldehyde derivatives such as p-anisaldehyde (chalcone A [(E)-4'-hydroxy-4-methoxychalcone]), veratraldehyde (chalcone B [(E)-4'-hydroxy-3,4-dimethoxychalcone]), 4-chlorobenzaldehyde (chalcone C [(E)-4'-hydroxy-4-chlorochalcone]) and 2,4-dihydroxyacetophenone with 4-chlorobenzaldehyde (chalcone D [(E)-2',4'-dihydroxy-4-chlorochalcone]) in methanol as solvent. The synthesis was carried out in alkaline condition (KOH) by stirring the mixture at room temperature for 48 h. The structures of products were identified by FTIR, GC-MS, 1H- and 13C-NMR spectrometers. The results showed that the chalcone derivatives (A-D) were yielded in 96; 97; 96; and 93%, respectively as yellow solid. The anticancer test indicated that the chalcone D was the most active towards T47D cell line with IC50 of 42.66 μg/mL and the chalcone C was the most active against WiDr cell line with IC50 of 20.42 μg/mL.


1992 ◽  
Vol 263 (2) ◽  
pp. C502-C508 ◽  
Author(s):  
W. S. Spielman ◽  
K. N. Klotz ◽  
L. J. Arend ◽  
B. A. Olson ◽  
D. G. LeVier ◽  
...  

We have previously reported that in several renal cell types, adenosine receptor agonists inhibit adenylyl cyclase and activate phospholipase C via a pertussis toxin-sensitive G protein. In the present study, in 28A cells, both of these adenosine receptor-mediated responses were inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a highly selective A1 adenosine receptor antagonist. The binding characteristics of the adenosine A1 receptor in the 28A renal cell line were studied using the radiolabeled antagonist [3H]DPCPX to determine whether two separate binding sites could account for these responses. Saturation binding of [3H]DPCPX to 28A cell membranes revealed a single class of A1 binding sites with an apparent Kd value of 1.4 nM and maximal binding capacity of 64 fmol/mg protein. Competition experiments with a variety of adenosine agonists gave biphasic displacement curves with a pharmacological profile characteristic of A1 receptors. Comparison of [3H]DPCPX competition binding data from 28A cell membranes with rabbit brain membranes, a tissue with well-characterized A1 receptors, reveals that the A1 receptor population in 28A cells has similar agonist binding affinities to the receptor population in brain but has a considerably lower density. Addition of guanosine 5'-triphosphate (100 microM) to 28A cell membranes caused the competition curves to shift from biphasic to monophasic, indicating that the A1 receptors exist in two interconvertible affinity states because of their coupling to G proteins.(ABSTRACT TRUNCATED AT 250 WORDS)


2021 ◽  
Vol 18 (1) ◽  
pp. 38-46
Author(s):  
Juwita Rahmawati ◽  
Maryati Maryati

Avocado plants are widely used as traditional medicine in Indonesia. This research aimed to determine the cytotoxic and antiproliferation activity of avocado seed extract and fractions on the T47D breast cancer cell line. Extraction was done by maceration method using 96% ethanol, then fractionation was done by liquid-liquid partition using n-hexane, chloroform, and ethyl acetate. Cytotoxic and antiproliferation tests were done by the MTT method. Apoptosis activity was investigated by the double staining method, using acridine orange-propidium iodide as a staining reagent. Results showed that the n-hexane fraction of avocado seed had a cytotoxic activity with IC50 27.9 µg/mL. N-hexane fraction of avocado seed inhibited proliferation and induced apoptosis of T47D cell line.


F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 168
Author(s):  
Woro Anindito Sri Tunjung ◽  
Puspa Restu Sayekti

Background: Breast cancer is the second leading cause of death in women. Alternative medicine with high efficacy is needed for breast cancer treatments, for example induction of apoptosis using natural products. It has been found that many natural apoptosis-inducing compounds are isolated from marine sponge. The objective of this study is to analyze the ability of extracts of the sponge Ancorina sp. to induce apoptosis on human breast cancer T47D cell line and find out its mechanism. Methods: T47D cells were treated with crude extracts of methanol, dichloromethane:methanol (1:1) and dichloromethane Ancorina sp. for 24 h, and doxorubicin was used as a positive control. Methods used for this study were MTT assay to examine cell viability and determine IC50 of the three extracts, while the percentage of apoptosis and caspase-3 were investigated by flow cytometry. Results: IC50 values of methanol, dichloromethane:methanol (1:1), and dichloromethane extract were 84.25, 121.45, and 99.85μg/mL respectively. The percentages of apoptotic cells after treatment with methanol, dichloromethane:methanol (1:1), and dichloromethane extracts were 88.68, 27.54 and 53.63% respectively, whereas the percentage of caspase-3 was 77.87, 12.66 and 12.97%, respectively. Conclusions: These results revealed that all extracts of Ancorina sp. have strong or moderate cytotoxicity and have the ability to induce apoptosis on T47D human breast cancer cell line. However, methanol crude extract has high efficacy to induce apoptosis through caspase-3 activation compared to the other extracts. Hence methanol extract warrants further investigation as a natural medicine for human breast cancer.


2019 ◽  
Vol 19 (4) ◽  
pp. 1081
Author(s):  
Artania Adnin Tri Suma ◽  
Tutik Dwi Wahyuningsih ◽  
Mustofa Mustofa

The synthesis of N-phenylpyrazolines 1-5 was performed by the cyclocondensation of phenylhydrazine and appropriate chalcones that have been synthesized from our previous work. All of the compounds were elucidated for their structure using GC-MS, FTIR, 1H, and 13C-NMR spectrometers. Their anticancer activity was evaluated against breast cancer cell line (T47D) and colorectal cancer cell line (WiDr). Compound 4 (4-(3-(4-chlorophenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-5-yl)-2-methoxyphenol) was found to be the most potent compound with IC50 value of 13.11 µg/mL in T47D cell line and 3.29 µg/mL in WiDr cell line. Docking study was conducted to evaluate the interaction between all compounds and EGFR receptor on cancer cells. Among the tested compounds, compound 4 is the only compound that has interaction with MET769 residue through hydrogen bonding due to the presence of hydroxyl group on its structure. Our findings suggest that the synthesized N-phenylpyrazolines in this study have a promising anticancer activity.


Sign in / Sign up

Export Citation Format

Share Document