scholarly journals PGV-0 AND PGV-1 INCREASED APOPTOSIS INDUCTION OF DOXORUBICIN ON MCF-7 BREAST CANCER CELLS

2015 ◽  
Vol 12 (2) ◽  
pp. 55-59
Author(s):  
Edy Meiyanto
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agent ◽  
Apoptosis Induction ◽  
Single Treatment ◽  
Cell Cycle Modulation ◽  
Induced Apoptosis ◽  
Mcf 7

As chemotherapeutic backbone for breast cancer therapy, doxorubicin showed various side effects and induced resistancy of breast cancer cells. Development of targeted therapy on breast cancer focused on combinatorial therapy of doxorubicin and molecular targeted agents. PGV-0 and PGV-1, a curcumin analogue showed potency as co-chemotherapeutic agent with doxorubicin. Our previous study of PGV-0 and PGV-1 showed cytotoxic activity in T47D cells. Therefore, the aim of this research is to examine the synergistic effect of PGV-0, PGV-1 on the cytotoxic activity of doxorubicin through cell cycle modulation and apoptotic induction on MCF-7 breast cancer cell lines. The cytotoxic assay of PGV-0, PGV-1, doxorubicin, and their combination were carried out by using MTT assay. Cell cycle distribution and apoptosis were determined by flowcytometer FACS-Calibur and the flowcytometry data was analyzed using Cell Quest program. Single treatment of PGV-0, PGV-1 and doxorubicin showed cytotoxic effect on MCF-7 with cell viability IC50 value 50 µM, 6 µM and 350 nM respectively. Single treatment of Doxorubicin 175 nM induced G2/M arrest. Single treatment of PGV-0 5 µM induced G2/M arrest while in higher dose 12.5  µM, PGV-0 induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 5 µM induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 12.5 µM also increased apoptosis induction. Single treatment of PGV-1 0.6 µM induced G1 arrest while in higher dose 1.5  µM, PGV-1 induced apoptosis. Combination of doxorubicin 175 nM and PGV-1 0.6 µM induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 1.5 µM also increased apoptosis induction. PGV-0 and PGV-1 are potential to be delevoped as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle modulation, but the molecular mechanism need to be explored detail.  Key words: PGV-0, PGV-1, doxorubicin, co-chemotherapy, breast cancer, cell cycle arrest, apoptosis

scholarly journals COMBINATION OF HEDYOTIS CORYMBOSA L. AND TINOSPORA CRISPA ETHANOLIC EXTRACT INCREASE CISPLATIN CYTOTOXICITY ON T47D BREAST CANCER CELLS

2018 ◽  
Vol 11 (7) ◽  
pp. 171 ◽  
Author(s):  
Rollando Rollando
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cytotoxic Effect ◽  
Ethanolic Extract ◽  
T47d Cell ◽  
Apoptosis Induction ◽  
Cell Accumulation ◽  
Cell Cycle Modulation

Objective: Ursolic acid was a compound found in Hedyotis corymbosa L., (HCoL) while berberine found in Tinospora crispa (TCa) which are proven to have cytotoxic effect to cancer cells. This research aims to review the effect of cisplatin, ethanolic extract of HCoL and TCa to the sensitivity increase on breast cancer cells, which will be confirmed through apoptosis induction and cell cycle modulation.Methods: The cytotoxic effect was tested using 3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide assay on T47D cell using the IC50 parameter. The combination was tested by determining their combination index (CI) and cell viability. The combination effect of apoptosis induction and cell cycle modulation was observed using flow cytometry method.Results: The cytotoxic test result of the combination shows CI value of below 1 at the concentration of HCoL ethanolic extract as much as 1 μg/mL, TCa ethanolic extract as much as 6 μg/mL, and cisplatin as much as 2,5 μM. The combination of HCoL ethanolic extract, TCa ethanolic extract, and cisplatin results in phase S cell accumulation (29.98%) on breast cancer cell T47D and was able to induce apoptosis.Conclusion: The result proves that ethanolic extract of HCoL and TCa can be developed as a cochemotherapeutic agent with cisplatin to increase the effectivity of breast cancer treatment.

scholarly journals Ursolic Acid Enhances Doxorubicin Cytotoxicity on MCF-7 Cells Mediated by G2/M Arrest

2012 ◽  
Vol 3 (3) ◽  
pp. 410
Author(s):  
Ibrahim Arifin ◽  
Adam Hermawan ◽  
Muthi' Ikawati ◽  
Sari Haryanti ◽  
Anindyajati Anindyajati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agent ◽  
Ic50 Value ◽  
Combinational Treatment ◽  
Mcf 7

Ursolic acid has been widely known to possess biological activity against numerous tumor cell lines. Previous studies revealed its cytotoxicity on several cancer cells in vitro by either inducing apoptosis or cell cycle modulation. This study was conducted to investigate ursolic acid’s cytotoxicity solely and in combination with a chemotherapeutic agent, doxorubicin, on MCF-7 breast cancer cells, followed by observation on its mechanism. Cytotoxicity of single and combinational treatment of ursolic acid and doxorubicin on MCF-7 breast cancer cells were conducted by using MTT assay. Single treatment was then evaluated by determining IC50 value, while combinational treatment was evaluated by analyzing cell viability and evaluating combination index (CI). To explore the mechanism underlying cytotoxic effect on respected cells, further analysis on cell cycle profile of single and combinational treatment was conducted by flow cytometry. Twenty four hours treatment of ursolic acid inhibited MCF-7 cells’ growth with IC50 value of 37 µM, while combinational treatment showed that several concentration combinations of ursolic acid and doxorubicin exhibited synergism of cytotoxic activity on MCF-7 cells, giving optimum CI value of 0.54. Flow cytometric analysis showed that combinational treatment induced G2/M arrest in MCF-7 cells. These results show that ursolic acid is promising to be developed as either single chemopreventive agent, or as doxorubicin’s co-chemotherapeutic agent in breast cancer treatment. Observation on the selectivity as part of safety aspect together with in silico, in vitro, and in vivo study on its molecular mechanism should be conducted.Keywords: ursolic acid, doxorubicin,co-chemotherapeutic agent, breast cancer, cell cycle

scholarly journals PRODH/POX-Dependent Celecoxib-Induced Apoptosis in MCF-7 Breast Cancer

2021 ◽  
Vol 14 (9) ◽  
pp. 874
Author(s):  
Magdalena Misiura ◽  
Ilona Ościłowska ◽  
Katarzyna Bielawska ◽  
Jerzy Pałka ◽  
Wojciech Miltyk
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cells ◽  
Collagen Biosynthesis ◽  
Proline Metabolism ◽  
Energetic Metabolism ◽  
Induced Apoptosis ◽  
Mcf 7

Celecoxib (Cx), an inhibitor of cyclooxygenase 2, induces apoptosis of cancer cells. However, the mechanism of the chemopreventive effect remains not fully understood. We aimed to investigate the role of PRODH/POX that is involved in the regulation of apoptosis induced by celecoxib. MCF-7 breast cancer cell line and the corresponding MCF-7 cell line with silenced PRODH/POX (MCF-7shPRODH/POX) were used. The effects of Cx on cell viability, proliferation, and cell cycle were evaluated. The expressions of protein markers for apoptosis (Bax, caspase 9, and PARP) and autophagy (Atg5, Beclin 1, and LC3A/B) were investigated by Western immunoblotting. To analyze the proline metabolism, collagen biosynthesis, prolidase activity, proline concentration, and the expression of proline-related proteins were evaluated. The generation of ATP, ROS, and the ratio of NAD+/NADH and NADP+/NADPH were determined to test the effect of Cx on energetic metabolism in breast cancer cells. It has been found that Cx attenuated MCF-7 cell proliferation via arresting the cell cycle. Cx induced apoptosis in MCF-7 breast cancer cells, while in MCF-7shPRODH/POX, autophagy occurred more predominantly. In MCF-7 breast cancer cells, Cx affected proline metabolism through upregulation of proline biosynthesis, PRODH/POX and PYCRs expressions, PEPD activity, and downregulation of collagen biosynthesis. In MCF-7shPRODH/POX clones, these processes, as well as energetic metabolism, were remarkably suppressed. The data for the first time suggest that celecoxib induces apoptosis through upregulation of PRODH/POX in MCF-7 breast cancer cells.

scholarly journals Mutant p53L194F Harboring Luminal-A Breast Cancer Cells Are Refractory to Apoptosis and Cell Cycle Arrest in Response to MortaparibPlus, a Multimodal Small Molecule Inhibitor

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3043
Author(s):  
Ahmed Elwakeel ◽  
Anissa Nofita Sari ◽  
Jaspreet Kaur Dhanjal ◽  
Hazna Noor Meidinna ◽  
Durai Sundar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Small Molecule ◽  
Breast Cancer Cells ◽  
Luminal A ◽  
Molecular Analyses ◽  
Cycle Arrest ◽  
Mcf 7

We previously performed a drug screening to identify a potential inhibitor of mortalin–p53 interaction. In four rounds of screenings based on the shift in mortalin immunostaining pattern from perinuclear to pan-cytoplasmic and nuclear enrichment of p53, we had identified MortaparibPlus (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole) as a novel synthetic small molecule. In order to validate its activity and mechanism of action, we recruited Luminal-A breast cancer cells, MCF-7 (p53wild type) and T47D (p53L194F) and performed extensive biochemical and immunocytochemical analyses. Molecular analyses revealed that MortaparibPlus is capable of abrogating mortalin–p53 interaction in both MCF-7 and T47D cells. Intriguingly, upregulation of transcriptional activation function of p53 (as marked by upregulation of the p53 effector gene—p21WAF1—responsible for cell cycle arrest and apoptosis) was recorded only in MortaparibPlus-treated MCF-7 cells. On the other hand, MortaparibPlus-treated T47D cells exhibited hyperactivation of PARP1 (accumulation of PAR polymer and decrease in ATP levels) as a possible non-p53 tumor suppression program. However, these cells did not show full signs of either apoptosis or PAR-Thanatos. Molecular analyses attributed such a response to the inability of MortaparibPlus to disrupt the AIF–mortalin complexes; hence, AIF did not translocate to the nucleus to induce chromatinolysis and DNA degradation. These data suggested that the cancer cells possessing enriched levels of such complexes may not respond to MortaparibPlus. Taken together, we report the multimodal anticancer potential of MortaparibPlus that warrants further attention in laboratory and clinical studies.

Novel Platinum(II) Complexes Selectively Induced Apoptosis and Cell Cycle Arrest of Breast Cancer Cells In Vitro

2019 ◽  
Vol 4 (44) ◽  
pp. 12971-12977
Author(s):  
Nenad Marković ◽  
Milan Zarić ◽  
Marija D. Živković ◽  
Snežana Rajković ◽  
Ivan Jovanović ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cycle Arrest ◽  
Induced Apoptosis

scholarly journals A polysaccharide from Huaier induced apoptosis in MCF-7 breast cancer cells via down-regulation of MTDH protein

2016 ◽  
Vol 151 ◽  
pp. 1027-1033 ◽  
Author(s):  
Zhiyong Luo ◽  
Xiaopeng Hu ◽  
Hua Xiong ◽  
Hong Qiu ◽  
Xianglin Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Down Regulation ◽  
Induced Apoptosis ◽  
Mcf 7

Effet radiosensibilisateur de l'acide linoléique conjugué chez les cellules cancéreuses du sein MCF-7 et MDA-MB-231

2004 ◽  
Vol 82 (2) ◽  
pp. 94-102 ◽  
Author(s):  
Geneviève Drouin ◽  
Annie Douillette ◽  
Pierre Lacasse ◽  
Benoit Paquette
Keyword(s):  
Breast Cancer ◽  
Linoleic Acid ◽  
Cancer Cells ◽  
Conjugated Linoleic Acid ◽  
Breast Cancer Cells ◽  
Fold Increase ◽  
Breast Cancer Cell Lines ◽  
Apoptotic Pathways ◽  
Induced Apoptosis ◽  
Mcf 7

Apoptotic pathways in breast cancer cells are frequently altered, reducing the efficiency of radiotherapy. Conjugated linoleic acid (CLA), known to trigger apoptosis, was tested as radiosensitizer in breast cancer cells MCF-7 and MDA-MB-231. The CLA-mix, made up of the isomers CLA-9cis 11trans and CLA-10trans 12cis, was compared to three purified isomers, i.e., the CLA-9cis 11cis, CLA-9cis 11trans, and CLA-10trans 12cis. Using the apoptotic marker YO-PRO®-1, the CLA-9cis 11cis at 50 µmol/L turned out to be the best apoptotic inducer leading to a 10-fold increase in MCF-7 cells and a 2,5-fold increase in MDA-MB-231 cells, comparatively to the CLA-mix. Contrary to previous studies on colorectal and prostate cancer cells, CLA-10trans 12cis does not lead to an apoptotic response on breast cancer cell lines MCF-7 and MDA-MB-231. Our results also suggest that the main components of the CLA-mix (CLA-9cis 11trans and CLA-10trans 12cis) are not involved in the induction of apoptosis in the breast cancer cells studied. A dose of 5 Gy did not induce apoptosis in MCF-7 and MDA-MB-231 cells. The addition of CLA-9cis 11cis or CLA-mix has allowed us to observe a radiation-induced apoptosis, with the CLA-9cis 11cis being about 8-fold better than the CLA-mix. CLA-9cis 11cis turned out to be the best radiosensitizer, although the isomers CLA-9cis 11trans and CLA-10trans 12cis have also reduced the cell survival following irradiation, but using a mechanism not related to apoptosis. In conclusion, the radiosensitizing property of CLA-9cis 11cis supports its potential as an agent to improve radiotherapy against breast carcinoma.Key words: breast cancer, conjugated linoleic acid (CLA), radiotherapy, apoptosis.

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