scholarly journals Ethanolic Extract of Secang (Caesalpinia sappan L.) Wood Performs as Chemosensitizing Agent Through Apoptotic Induction on Breast Cancer MCF-7 Cells

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.  

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Min Sung Kim ◽  
Chul Won Lee ◽  
Jung-Hoon Kim ◽  
Jang-Cheon Lee ◽  
Won Gun An

Rhus verniciflua Stokes has long been used as a food supplement and traditional herbal medicine for various ailments in East Asia. We evaluated the anticancer effects of Rhus verniciflua Stokes extract (RVSE) on MCF-7 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, annexin V/7-AAD staining, and western blotting. In addition, the gallic acid content of RVSE was assayed using high-performance liquid chromatography. RVSE inhibited the growth of MCF-7 cells in a dose-dependent manner by inducing apoptosis in the sub-G1 phase. RVSE also significantly increased the number of apoptotic cells and increased the expression of p53 and p21 in a dose-dependent manner. Furthermore, RVSE treatment increased the Bax:Bcl-2 ratio and the levels of apoptosis-related factors, such as cleaved caspase-3 and -9 and PARP, in MCF-7 cells. Our findings suggest that the proapoptotic effect of RVSE on MCF-7 cells is mediated by p53, p21, and the intrinsic mitochondrial cascade. Thus, RVSE shows promise for the prevention and treatment of breast cancer.


Author(s):  
Ika Nurzijah ◽  
Dyaningtyas Dewi Pamungkas Putri ◽  
Erlina Rivanti ◽  
Edy Meiyanto

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


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


Author(s):  
Nur Dina Amalina ◽  
Meiny Suzery ◽  
Bambang Cahyono

Hyptis pectinata (L.) poit, popularly known in the world as “comb bushmint” is a medicinal plant commonly used for the treatment of throat and skin inflammations, bacterial infection, pain and cancer. The objective of this research is to determine the cytotoxic and antiproliferative effect under Hyptis pectinata ethanolic extract (HPE) treatment on breast cancer cells. The effect HPE of on cytotoxicity was examined by MTT assay on MCF-7 breast cancer cells. This assay also used to determine cell proliferation over 3 days of treatment with 1.5 – 100 µg/mL HPE. HPE showed that exhibited cytotoxic effects with IC50 value of 30 µg/mL for 24 hours and changes the physiological morphology on MCF-7 cells. Interestingly, the treatment of HPE for 48 and 72 hours highly decreases cell viability on MCF-7 with dose and time-dependent manner compared to untreated cells. These results indicate that HPE has antiproliferative activities and maybe the potential to be developed as a natural chemotherapeutic agent.Keywords: Hyptis pectinata (L.) poit extract, cytotoxicity, antiproliferative, MCF-7 cells


2021 ◽  
Vol 26 (3) ◽  
pp. 133
Author(s):  
Dhania Novitasari ◽  
Laeli Muntafiah ◽  
Nur Fitra Sari ◽  
Edy Meiyanto ◽  
Adam Hermawan

One of the mechanisms of cancer cell resistance toward chemotherapy is through cancer stem cells (CSCs), which are characterized by excessive activation of regulator proteins such as human epidermal receptor 2 (HER2). Sappan wood (Caesalpinia sappan L.) contains brazilin and brazilein that exhibit cytotoxic effects on several cancer cell lines. We aimed to explore the potency of the ethanolic extract of sappan (EES) in CSCs through bioinformatic analyses and by using a three-dimensional (3D) breast cancer stem cells (BCSCs) for in vitro assay with two different models (i.e., BCSCs and HER2-BCSCs) in order to identify the potential therapeutic targets of genes (PTTGs). Bioinformatic analyses identified PTTGs, which were further analyzed by gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction (PPI) networks, and hub protein selection. Mammospheres were cultured under conditioned media. The cytotoxic effects of EES were then measured by direct counting and based on the mammosphere-forming potential (MFP). Bioinformatic analysis disclosed PIK3CA and TP53 as PTTGs in BCSCs and HER2-BCSCs, respectively. In addition, the KEGG pathway analyses also demonstrated that PTTGs could regulate the ERBB pathway. EES thus demonstrated cytotoxicity and inhibited the formation of mammospheres. Collectively, EES exhibited excellent potential for further development as an inhibitor of cancer stem cells in breast cancer.


Author(s):  
Rahmawaty Rachmady ◽  
Laely Muntafiah ◽  
Fahmi Rosyadi ◽  
Imroatus Sholihah ◽  
Sri Handayani ◽  
...  

Human Epidermal Growth Factor Receptor 2 (HER2) plays critical role in the initiation of breast cancer cell proliferation. Inhibition of HER2 overexpression is a promising strategy in the treatment of breast cancer. One of the potential natural substances that possess cytotoxic in cancer cells is Secang (Caesalpinia sappan L.). Ethanolic extract of secang heartwood containing brazilein and brazilin shows cytotoxic effect on various cancer cells. Thus this research aims to determine the proliferative inhibition activity of secang heartwood ethanolic extract (SEE) through HER2 expression on MCF-7/HER2 positive. Cytotoxic activity of SEE on MCF-7/HER2 positive cells was observed by MTT assay, meanwhile the inhibition activity of  HER2 on MCF-7/HER2 cells was determined by immunofluoresence assay. Furthermore, to confirm the possible mechanism of brazilein and brazilin for its cytotoxic activity was studied through molecular docking using PLANTS software. Based on this study, SEE exhibited cytotoxic effect on MCF-7/HER2 positive cells with IC50 value of 25 µg/ml, and EES also inhibited HER2 expression, indicated that the antiproliferative effect of SEE was possible through the inhibition of HER2. Docking score of brazilein, brazilin, and native ligand on HER2 were -77; -73; -120 respectively, showed the affinity of brazilein in HER2 was lower than affinity of native ligand, but they had specific amino acid to interaction. Hence, SEE can be developed as one of promising chemopreventive agent from natural products.Keywords: Caesalpinia sappan L., cytotoxic, immunofluorescence, molecular docking, MCF7/HER2 cells


Author(s):  
Hilyatul Fadliyah ◽  
Nindya Budiana Putri ◽  
Ziana Walidah ◽  
Ika Putri Nurhayati ◽  
Muthi Ikawati ◽  
...  

                The development of cancer at an advanced stage is signed with metastasis that trigger the high of mortality caused breast cancer, possitive HER2 type mainly. Boesenbergia pandurata known as medicinal plant possessing anticancer potential due to the cytototoxic and antimetastatic characteristic of its active compound. The aim of this study is to observe the inhibitory of migration of Boesenbergia pandurata ethanolic extract (BPEE) in combination with doxorubicin (Dox) on MCF-7/HER2 cells. BPEE was prepared by 96% ethanol maceration. Under MTT assay, BPEE decreased the cells viability with IC50 value of 23 ± 3.9 μg/mL. Lamellipodia and wound healing assay analysis showed that BPEE (5 μg/mL) and its combination with doxorubicin (10 nM) inhibited cells migration after 48 hours observation, while gelatin zymography analysis showed that this combination did not affect the expression of MMP2 and MMP9 proteins, but single treatment of BPEE was more able to decrease the expression of both MMP. The combination with those concentrations inhibited the cells migration but not with the cells viability. Thus, BPEE is potential to be developed as antimetastatic agent. The mechanism itself needs to be explored further.


2021 ◽  
Vol 7 (3) ◽  
pp. 188
Author(s):  
Ji-In Noh ◽  
Seul-Ki Mun ◽  
Eui Hyeon Lim ◽  
Hangun Kim ◽  
Dong-Jo Chang ◽  
...  

Physconia hokkaidensis methanol extract (PHE) was studied to identify anticancer effects and reveal its mechanism of action by an analysis of cytotoxicity, cell cycles, and apoptosis biomarkers. PHE showed strong cytotoxicity in various cancer cells, including HL-60, HeLa, A549, Hep G2, AGS, MDA-MB-231, and MCF-7. Of these cell lines, the growth of MDA-MB-231 was concentration-dependently suppressed by PHE, but MCF-7 was not affected. MDA-MB-231 cells, triple-negative breast cancer (TNBC) cells, do not express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), whereas MCF-7 cells are ER-positive, PR-positive, and HER-2-negative breast cancer cells. The number of cells in sub-G1 phase was increased after 24 h of treatment, and annexin V/PI staining showed that the population size of apoptotic cells was increased by prolonged exposure to PHE. Moreover, PHE treatment downregulated the transcriptional levels of Bcl-2, AMPK, and p-Akt, whereas it significantly upregulated the levels of cleaved caspase-3, cleaved caspase-9, and cleaved-PARP. In conclusion, it was confirmed that the PHE exhibited selective cytotoxicity toward MDA-MB-231, not toward MCF-7, and its cytotoxic activity is based on induction of apoptosis.


2018 ◽  
Vol 19 (2) ◽  
pp. 54-61
Author(s):  
Ahmad Khanifudin ◽  
Gian Primahana ◽  
Sylvia Rizky Prima ◽  
Puspa Dewi Lotulung ◽  
Muhammad Hanafi

Cinchonine is a type of cinchona alkaloid compound commonly found and/or isolated from Cinchona sp. plant. It is commonly used to treat malaria, and can potentially be used against cancer cells. In this particular study, cinchonine ester derivatives were extracted through esterification processs. Synthesized esther is aimed to gain higher lipophilicity of cinchonine so that makes it easier to pass through cell membrane. Esterification was done using DCC activator as well as DMAP catalyst with tiglic acid used to create cinchonine tiglat. Subsequent cinchonine tiglat was obtained in the form of oil with 25,28% yield. The compound obtained from the synthesis was the analyzed using LC-ESI-MS and 1H-NMR spectroscopy instrumentation. Results show that the target compound has been successfully synthesized. Its cytotoxic ability against MCF-7 breast cancer cells was tested using the Alamar Blue method. Results concluded that cinchonine tiglat ester compound has a viable cytotoxic activity with IC50 value of 1.22 ppm.


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