scholarly journals Cytotoxic and Apoptotic-inducing Effect of Fraction Containing Brazilein from Caesalpinia sappan L. and Cisplatin on T47D Cell Lines

Author(s):  
Prisnu Tirtanirmala ◽  
Annisa Novarina ◽  
Rohmad Yudi Utomo ◽  
Raisatun Nisa Sugiyanto ◽  
Riris Istighfari Jenie ◽  
...  

Anticancer activity of secang’s heartwood (Caesalpinia sappan L.) is based on its main compound: brazilin and brazilein. Brazilin, brazilein, and other compounds such as caesalpiniaphenol can affect proteins that have a role in apoptosis. In this study, we observed cytotoxic activity of fraction containing brazilein (FCB) alone or in combination with chemotherapeutic agent, cisplatin and the ability of the combination to induce apoptosis in T47D breast cancer cell lines. Cytotoxicity assay was determined using MTT assay, whereas the detection apoptosis induction was conducted using flow cytometry using Annexin-V and propidium iodide. FCB and cisplatin showed cytotoxic effect on T47D cells with IC50 value of 68 µg/mL and 16 µM, respectively. Combination of FCB and cisplatin result synergistic combination at the concentration ratio of 1/2 IC50 with CI value of 0.66. Its combination also able to induce apoptosis on T47D cell population 13% larger than the single treatment. Based on this study, we conclude that FCB is able to enhance the cytotoxic effects of cisplatin by inducing apoptosis.Keywords:  Caesalpinia sappan L., cisplatin, apoptosis, breast cancer

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2610 ◽  
Author(s):  
Joanna Jinling Lee ◽  
Latifah Saiful Yazan ◽  
Nur Kartinee Kassim ◽  
Che Azurahanim Che Abdullah ◽  
Nurulaidah Esa ◽  
...  

Christia vespertilionis, commonly known as ‘Daun Rerama’, has recently garnered attention from numerous sources in Malaysia as an alternative treatment. Its herbal decoction was believed to show anti-inflammatory and anti-cancer effects. The present study investigated the cytotoxicity of the extract of root and leaf of C. vespertilionis. The plant parts were successively extracted using the solvent maceration method. The most active extract was further fractionated to afford F1–F8. The cytotoxic effects were determined using MTT assay against human breast carcinoma cell lines (MCF-7 and MDA-MB-231). The total phenolic content (TPC) of the extracts were determined. The antioxidant properties of the extract were also studied using DPPH and β-carotene bleaching assays. The ethyl acetate root extract demonstrated selective cytotoxicity especially against MDA-MB-231 with the highest TPC and antioxidant properties compared to others (p < 0.05). The TPC and antioxidant results suggest the contribution of phenolic compounds toward its antioxidant strength leading to significant cytotoxicity. F3 showed potent cytotoxic effects while F4 showed better antioxidative strength compared to others (p < 0.05). Qualitative phytochemical screening of the most active fraction, F3, suggested the presence of flavonoids, coumarins and quinones to be responsible toward the cytotoxicity. The study showed the root extracts of C. vespertilionis to possess notable anti-breast cancer effects.


2021 ◽  
Author(s):  
Hee-Jeong Lee ◽  
Cheol-Hee Choi

Abstract BackgroundAlthough several novel resistant breast cancer cell lines have been established, only a few resistant breast cancer cell lines overexpress breast cancer resistance proteins (BCRP). The aim of this study was to establish new resistant breast cancer cell lines overexpressing BCRP using SN38 (7-ethyl-10-hydroxycamptothecin), an active metabolite of irinotecan and was to discover genes and mechanisms associated with multidrug resistance.MethodsSN38-resistant T47D breast cancer cell sublines were selected from the wild-type T47D cells by gradually increasing SN38 concentration. The sensitivity of the cells to anti-cancer drugs was assessed by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Expression profiles of the resistance-related transporters were examined using the resistance diagnostic kit (Drugsporter®), real time RT-PCR, and western blot analysis. Intracellular drug accumulation in the resistant cells was determined using flow cytometry.ResultsThe SN38-resistant T47D breast cancer cell sublines T47D/SN120 and T47D/SN150 were established after long-term exposure (more than 16 months) of wild-type T47D cells to 120 nM and 150 nM SN38, respectively. T47D/SN120 and T47D/SN150 cells were more resistant to SN38 (14.5 and 59.1 times, respectively), irinotecan (1.5 and 3.7 times, respectively), and topotecan (4.9 and 12 times, respectively), than the wild-type parental cells. Both T47D/SN120 and T47D/SN150 sublines were cross-resistant to various anti-cancer drugs. These resistant sublines overexpressed mRNAs of MRP1, MRP2, MRP3, MRP4, and BCRP. The DNA methylase inhibitor 5-aza-2'-deoxycytidine and the histone deacetylase inhibitor trichostatin A increased the expression levels of BCRP, MRP1, MRP2, MRP3, and MRP4 transcripts in T47D/WT cells. Drug accumulation was found to be lower in T47D/SN120 and T47D/SN150 cells, compared to that in T47D/WT cells. However, treatment with known chemosensitizers increased the intracellular drug accumulation and sensitivity of anti-tumor agents.ConclusionT47D/SN120 and T47D/SN150 cells overexpressed MRP1, MRP2, MRP3, MRP4, and BCRP due to the suppression of epigenetic gene silencing via DNA hypermethylation and histone deacetylation. Although these resistant cells present a higher resistance to various anti-cancer drugs than their parental wild-type cells, multidrug resistance was overcome by treatment with chemosensitizers. These SN38 resistant T47D breast cancer cell sublines expressing resistance proteins can be useful for the development of new chemosensitizers.


2012 ◽  
Vol 40 (2) ◽  
pp. 1655-1663 ◽  
Author(s):  
Anna Wyrębska ◽  
Jacek Szymański ◽  
Katarzyna Gach ◽  
Justyna Piekielna ◽  
Jacek Koszuk ◽  
...  

Author(s):  
Rahmi Khamsita ◽  
Adam Hermawan ◽  
Dyaningtyas Dewi Pamungkas Putri ◽  
Edy Meiyanto

Resistance to chemotherapy is believed to cause treatment failure of the patient cancer. Secang (Caesalpinia sappan L.) has been proven to possess anticancer activity on some cancer cell lines. The aimed of this study to develop ethanolic extract of secang wood (EES) as chemosensitizing agent through apoptotic induction on breast cancer MCF-7 cells. Extraction of secang was done by using maceration with 70 % ethanol. Single and combinatorial treatment of EES and doxorubicin on MCF-7 breast cancer cells were analyzed by using MTT assay to determine the IC50 value and combination index (CI) to evaluate the combinatorial effect. Apoptosis was analyzed with flowcytometry (annexin V).  EES showed a dose-dependent cytotoxicity (IC50 value of 37 µg/ml), while combinatorial treatment showed that 7 concentrations was found to be synergist with doxorubicin on MCF-7 cells. Combinatorial treatment also triggered apoptotic instead of single treatment. Based on this result, we conclude that ethanolic extract of secang wood is potential as chemosensitizing agent in breast cancer.Keywords: Caesalpinia sappan L, MCF-7 cells, doxorubicin, apoptosis.  


Author(s):  
Rohmad Yudi Utomo ◽  
Annisa Novarina ◽  
Prisnu Tirtanirmala ◽  
Ria Fajarwati Kastian ◽  
Riris Istighfari Jenie

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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