Secang (Caesalpinia sappan L.) Heartwood Ethanolic Extract Shows Activity as Doxorubicin Co-chemotherapeutic Agent by Apoptotis Induction on T47D Breast Cancer Cells

Doxorubicin, primary chemoteurapeutic agent used for breast cancer treatment, is known to have various side effects included multi drug resistance (MDR) phenomenon. Therefore, exploration of co-chemotherapeutic agent is important to be conducted in order to prevent MDR. Secang (Caesalpinia sappan L.) which contains active compounds brazilin and brazilein, is proven to have activity as anticancer. The aim of this study is to determine the potency of Caesalpinia sappan L. ethanolic extract (CEE) as co-chemotherapeutic agent of doxorubicin and its mechanism through apoptosis induction on T47D breast cancer cells. Caesalpinia sappan L. heartwood powder was macerated with ethanol 70%. The cytotoxic effect of CEE alone and its combination with doxorubicin was analyzed using MTT assay. Apoptosis assay was done by flowcytometry-annexin V method. CEE showed cytotoxic activity on T47D cells with IC50 value of 35 µg/ml, while combinatorial test showed that all of combination doses of CEE and doxorubicin gave synergistic effect. Flowcytometry-annexin V assay proved that treatment of CEE induced apoptosis of doxorubicin. Based on these results, we conclude that Caesalpinia sappan L. heartwood ethanolic extract is potential to be developed as co-chemotherapeutic agent of doxorubicin.Keywords : Caesalpinia sappan L., doxorubicin, apoptosis, T47D cells

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Enhancement of Cytotoxicity and Apoptosis Induction of Doxorubicin by Brazilein Containing Fraction of Secang (Caesalpinia sappan L.) on T47D Cells

Indonesian Journal of Cancer Chemoprevention ◽

10.14499/indonesianjcanchemoprev9iss1pp32-40 ◽

2018 ◽

Vol 9 (1) ◽

pp. 32

Author(s):

Rohmad Yudi Utomo ◽

Annisa Novarina ◽

Prisnu Tirtanirmala ◽

Ria Fajarwati Kastian ◽

Riris Istighfari Jenie

Keyword(s):

Breast Cancer Cells ◽

Chemotherapeutic Agent ◽

Annexin V ◽

T47d Cell ◽

Apoptosis Induction ◽

Binding Properties ◽

Caesalpinia Sappan ◽

T47d Cells ◽

Ic50 Value ◽

Induced Apoptosis

Combination chemotherapy (co-chemotherapy) is a recent strategy to reduce the toxicity effect and increase the effectivity of chemotherapeutic agent, such as Doxorubicin (Dox). Caesalpinia sappan L. are potential to be developed as co-chemoterapeutic agents due to its strong cytotoxicity toward several breast cancer cells. The purpose of this research is to observe the cytotoxicity of Brazilein containing fraction (BCF) in single and its combination with doxorubicin on T47D cells. BCF was obtained by fractionation using chloroform:ethyl acetate (40:60 v/v) as mobile phase. Molecular docking results showed that Brazilein and Brazilin interacted with Bcl-2 with different binding properties. Based on MTT assay, Dox and BCF performed potent cytotoxicity with IC50 value of 403 nM and 68 μg/mL, respectively. BCF increased the cytotoxicity of Dox and performed synergism with CI value <1 and decreased possible toxicity with DRI value>1. Under Annexin V PI staining Flowcytometry, BCF in single and its combination with doxorubicin induced apoptosis. In conclusion, single treatment of BCF and its combination with Dox performed cytotoxic effect and induced apoptosis on T47D cell lines.Keywords: Brazilein containing fraction, Doxorubicin, Co-chemoteraphy, Apoptosis, T47D cells

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Synergistic Combination of Ciplukan (Physalis angulata) Herbs Ethanolic Extract and Doxorubicin on T47D Breast Cancer Cells

Indonesian Journal of Cancer Chemoprevention ◽

10.14499/indonesianjcanchemoprev1iss1pp26-31 ◽

2010 ◽

Vol 1 (1) ◽

pp. 26

Author(s):

Inna Armandari ◽

Kartika Dyah Palupi ◽

Sofa Farida ◽

Adam Hermawan ◽

Ratna Asmah Susidarti ◽

...

Keyword(s):

Breast Cancer ◽

Cytotoxic Activity ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cardiac Toxicity ◽

Chemotherapeutic Agent ◽

Ethanolic Extract ◽

High Dose ◽

T47d Cells ◽

Ic50 Value

Doxorubicin is one of chemotherapeutic agent widely used in breast cancer treatment, but in high dose doxorubicin gives negative side effect, including vomit, nausea, immune suppression, and cardiac toxicity. This toxicity hopefully could be reduced by combination chemotherapy using natural herbs such as ciplukan herb. This research was conducted to explore cytotoxic activity of single ciplukan herbs ethanolic extract and its combination with doxorubicin on T47D breast cancer cells. Cytotoxic activity of ciplukan herbs ethanolic extract only and its combination with doxorubicin were tested on T47D cells using MTT assay to obtain IC50 value and combination index (CI), respectively. Single extract showed cytotoxic activity on T47D cells with IC50 value of was 160 µg/ml. Thus, combination treatment from ciplukan herbs ethanolic extract and doxorubicin showed synergistic effect (CI<1,0). This effect was reached at concentration of ciplukan herbs ethanolic extract-doxorubicin 80 μg/ml- 2 nM, 80 μg/ml-4 nM, and 80 μg/ml-8 nM. This research indicated that ciplukan herbs ethanolic extract is potential to be applied as co-chemotherapeutic agent in breast cancer therapy.Key word : ciplukan herbs, doxorubicin, co-chemotherapy, T47D cells

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

Pharmacon Jurnal Farmasi Indonesia ◽

10.23917/pharmacon.v12i2.32 ◽

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

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Combination of Curcuma (Curcuma xanthorriza Roxb) and Awar-awar (Ficus septica Burm.F.) Ethanolic Extracts Enhance Doxorubicin to Modulate Cell Cycle Progression of T47D Cells

Indonesian Journal of Cancer Chemoprevention ◽

10.14499/indonesianjcanchemoprev9iss1pp9-15 ◽

2018 ◽

Vol 9 (1) ◽

pp. 9

Author(s):

Laili Nailul Muna ◽

Riris Istighfari Jenie

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Breast Cancer Cells ◽

Cell Cycle Progression ◽

Chemotherapeutic Agent ◽

Ethanolic Extract ◽

Chemotherapeutic Agents ◽

Cycle Progression ◽

T47d Cells ◽

Cell Accumulation

One of the efforts to cure breast cancer is a combination of the chemotherapeutic agent with medicinal plants. This study was conducted to examine the activity of the combination between doxorubicin, curcuma rhizome (Curcuma xanthorriza Roxb.) ethanolic extract (CEE), and awar-awar leaves (Ficus septica Burm.f.) ethanolic extract (AAE) in inducing apoptosis and modulating the cell cycle progression in breast cancer T47D cells. The combination activity was performed using three series of concentration, 1/3; 1/6 and 1/12 of IC50, The combination index (CI) of doxorubicin, CEE and AEE was determined under MTT assay. The result showed that the combination of 10 µM, 5 µg/ml, 1 µg/ml concentrations of doxorubicin, CEE and AEE respectively result in synergistic effect with CI values less than 1. The treatment exhibited the cell accumulation in S phase (27.7%) against T47D breast cancer cells confirmed through cell cycle examination by flow cytometry. These results provided the evidence that CEE and the AEE can be developed as co-chemotherapeutic agents combined with doxorubicin to improve the effectiveness of breast cancer treatment.Keywords : Curcuma xanthorriza Roxb., Ficus septica Burm.f., doxorubicin, cell cycle.

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New curcumin analog, CCA-1.1, synergistically improves the antiproliferative effect of doxorubicin against T47D breast cancer cells

INDONESIAN JOURNAL OF PHARMACY ◽

10.22146/ijp.681 ◽

2020 ◽

pp. 244-256

Author(s):

Febri Wulandari ◽

Muthi' Ikawati ◽

Dhania Novitasari ◽

Mitsunori Kirihata ◽

Jun-ya Kato ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cytotoxic Activity ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cell Cycle Progression ◽

Synergistic Effects ◽

Annexin V ◽

Curcumin Analog ◽

T47d Cells

An improved compound of pentagamavunone-1 (PGV-1), chemoprevention-curcumin analog 1.1 (CCA-1.1), has been synthesized and proven to have antiproliferative effects against breast cancer cells. This study is designed to investigate the potency of CCA-1.1 alone and in combination with doxorubicin (Dox) on T47D cells in comparison with that of PGV-1. We used the MTT assay to assess cytotoxic activity. Propidium iodide (PI), annexin-V–PI, and DCFDA staining were respectively used to determine cell cycle profiles, apoptosis, and intracellular reactive oxygen species (ROS) levels. Senescent cells were identified using the SA-b-galactosidase assay. Our results revealed that CCA-1.1 possesses cytotoxic effects similar to those of PGV-1 on T47D cells. Synergistic effects during co-treatment with Dox were also observed. CCA-1.1 arrested cell cycle progression at the G2/M phase and limited sub-G1 accumulation, which is correlated with apoptosis. CCA-1.1 alone and in combination with Dox increased senescence and intracellular ROS to a similar level to those achieved by PGV-1. CCA-1.1 alone and in combination with Dox enhanced cytotoxic activity toward T47 cells compared to PGV-1. Thus, this curcumin analog may be a potential chemotherapeutic/co-chemotherapeutic candidate for estrogen receptor-positive (ER+) breast cancer therapy.

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Effect of Plectranthus amboinicus, Lour. Spreng. n-Hexane Extract on T47D Cells Line: Proliferation, Apoptosis and It’s Combination with Doxorubicine

Indonesian Journal of Pharmaceutical and Clinical Research ◽

10.32734/idjpcr.v3i1.3323 ◽

2020 ◽

Vol 3 (1) ◽

pp. 8-17

Author(s):

Poppy Anjelisa Zaitun Hasibuan ◽

Rosidah ◽

Pandapotan Nasution ◽

Syafruddin Ilyas

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

T47d Cell ◽

Hexane Extract ◽

Mediating Effect ◽

T47d Cells ◽

Plectranthus Amboinicus ◽

Induced Apoptosis ◽

Cytotoxicity Effects

The objectives of the study are to investigated the growth-inhibiting and apoptosis mediating effect of Plectranthus amboinicus (Lour.) Spreng n-hexane extract (PANE) on T47D cell lines. The assays were performed in the study were cytotoxicity assay and apoptosis induction of T47D cells. The cytotoxicity effects were determined by using MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide] assay. The effect of apoptosis were observed by ethidium bromide-acrydine orange method. The growth of T47D was inhibited by treatment with PANE on concentrations 20; 40; dan 80 µg/mL. The cell death (apoptosis) induced by PANE was characterized by orange fluorescent on the IC50 concentration. These results concluded that the n-hexane extract of Plectranthus amboinicus, (Lour.) Spreng. inhibited the growth of T47D breast cancer cells in dose and time dependent manners. PANE also could induced apoptosis on T47D breast cancer cells, but the combination of PANE-doxorubicine did not show the synergistic effect. The results suggesting that PANE may be a potent agent for the chemoprevention of breast cancer.

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Combination of Solanum nigrum L. Herb Ethanolic Extract and Doxorubicin Performs Synergism on T47D Breast Cancer Cells

Indonesian Journal of Cancer Chemoprevention ◽

10.14499/indonesianjcanchemoprev1iss2pp78-84 ◽

2010 ◽

Vol 1 (2) ◽

pp. 78 ◽

Cited By ~ 2

Author(s):

Anindyajati Anindyajati ◽

Sarmoko Sarmoko ◽

Dyaningtyas Dewi Pamungkas Putri ◽

Adam Hermawan ◽

Edy Meiyanto

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Chemotherapeutic Agent ◽

Ethanolic Extract ◽

Solanum Nigrum ◽

Breast Cancer Cell Lines ◽

Dependent Manner ◽

Combinational Treatment ◽

Solanum Nigrum L

Leunca (Solanum nigrum L.) has been proven to possess anticancer activity on some type of cancer cells. In vitro study of solamargine found in the herb showed cytotoxic effect against several breast cancer cell lines, such as T47D and MDA-MB-31. Hence, further study on its potential as a co-chemotherapeutic agent needs to be conducted, in order to overcome resistance problem commonly found in cancer chemotherapy. This study aimed to examine the cytotoxic activity of leunca herb ethanolic extract (LEE) alone and its combination with doxorubicin. Single and combinational treatment of LEE and doxorubicin on T47D breast cancer cells were done, and their viability representing cytotoxicity were analyzed by using MTT assay to determine the IC50 value and combination index (CI) to evaluate the combinational effect. Twenty four hours-treatment of LEE alone gave cytotoxicity activity showing a dose-dependent manner with the IC50 of 47 µg/ml, while combinational treatment showed that 4 µg/ml LEE was found to be synergist with 4 nM doxorubicin on T47D cells, with the optimum CI value of 0.59. This result shows that Solanum nigrum L. is potential to be proposed as doxorubicin co-chemotherapeutic agent against breast cancer. Further study on its molecular mechanism needs to be conducted.Key words: Solanum nigrum, doxorubicin, synergist, breast cancer

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Lobetyolin inhibits the proliferation of breast cancer cells via ASCT2 down-regulation-induced apoptosis

Human & Experimental Toxicology ◽

10.1177/09603271211021476 ◽

2021 ◽

pp. 096032712110214

Author(s):

Yansong Chen ◽

Ye Tian ◽

Gongsheng Jin ◽

Zhen Cui ◽

Wei Guo ◽

...

Keyword(s):

Breast Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Glutamine Metabolism ◽

Down Regulation ◽

Anti Cancer ◽

Induced Apoptosis ◽

Glutamine Uptake

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 ( SLC2A4), HK2 and PKM2 were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 ( SLC1A5), GLS1, GDH and GLUL were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. SLC1A5 knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. C-MYC knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3β signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake via down-regulating ASCT2. SLC1A5 knockdown attenuated the anti-cancer effect of lobetyolin. C-MYC knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect via ASCT2 down-regulation-induced apoptosis in breast cancer cells.

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