97 research outputs found
Increased ubiquitin-conjugation in cardiac myocytes and the involvement of crosstalk of G protein signaling
No full textIncreased ubiquitin-conjugation in cardiac myocytes and the involvement of crosstalk of G protein signaling
Full text link奈良先端科学技術大学院大学博士(バイオサイエンス)doctoral thesi
Caesalpinia sappan reduces the stemness of breast cancer stem cells involving the elevation of intracellular reactive oxygen species
No full textBackground and purpose: Breast cancer stem cells (BCSCs) as a kind of tumor cells are able to regenerate themselves, leading to apoptosis resistance and cancer relapse. It was reported that BCSCs contain lower levels of reactive oxygen species (ROS) associated with stemness capability. Caesalpinia sappan has been proposed for its chemopreventive potency against several cancer cells. This study aimed to evaluate the effects of Caesalpinia sappan extract (CSE) on cytotoxicity, apoptosis induction, ROS generation, and stemness markers of MDA-MB-231 and its BCSCs.
Experimental approach: Caesalpinia sappan was extracted under maceration with methanol. Magnetic-activated cell sorting was used to isolate BCSCs based on CD44+ and CD24- cell surface expression. The MTT test was used to assess the cytotoxic effects of CSE on MDA-MB-231 and BCSCs. Moreover, flow cytometry was used to examine the cell cycle distribution, apoptosis, ROS level, and CD44/CD24 level. Using qRT-PCR, the gene expression of the stemness markers NANOG, SOX-2, OCT-4, and c-MYC was assessed.
Findings/Results: We found that MDA-MB-231 contains 80% of the BCSCs population, and CSE showed more potent cytotoxicity toward BCSCs than MDA-MB-231. CSE caused apoptosis in MDA-MB-231 and BCSCs cells by increasing the level of ROS. Furthermore, CSE significantly reduced the MDA-MB-231 stemness marker CD44+/CD24- and the mRNA levels of pluripotent markers of cells in BCSCs.
Conclusion and implications: CSE potentially reduces BCSCs stemness, which may be mediated by the elevation of the ROS levels and reduction of the expression levels of stemness transcription
Aplikasi Ko-Kemoterapi Fraksi Etil Asetat Ekstrak Etanolik Daun Sambung Nyawa (Gynura procumbens (Lour.) Merr.) Pada Sel Kanker Payudara MCF-7
Full text linkCombination chemotherapy has been an interesting attention in recent years to cure cancer e.g. non-toxic or less toxic phytochemicals are being combined with chemo-therapeutic agents to sensitize cancer cell and to enhance the efficacy of chemothera-peutic agents as well as to reduce its toxicity to normal tissues. The aim of this research is to examine whether ethyl acetate fraction of Gynura procumbens ethanolic extract (SEF) synergizes the therapeutic potential of doxorubicin (Dox) on breast cancer cell line MCF-7. MTT assay were used to measure the growth inhibitory effect of the combination therapy on MCF-7 cells. SEF (5-250 µg/ml) treatment of cell resulted in 15-76% growth inhibition in a dose dependent manner (IC50 85 µg/ml), while Dox (10-100 nM) treatment did not show any inhibitory effect. The combina-tions of SEF (5-40µg/ml) with Dox (10-75 nM) seemed to not have any synergistic efficacy towards cell growth inhibition. Nevertheless, this result need further observa-tion regarding the IC50 of Dox on MCF-7 has not been determined yet. The cell characterization may influence the result. Doxorubicin could induce Akt survival apoptosis pathway in MCF-7 resulting resistancy of the cell towards doxorubicin
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
Full text linkOne 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
Ethanolic Extract of Hedyotis corymbosa L. Inhibits Migration and MMP-9 Activity on Metastatic Breast Cancer Cells
Full text linkMany natural products have been widely explored for their pharmacological activities, including anticancer activity. Hedyotis corymbosa L. is known for its anticancer properties toward several cancer cell lines. The study aims to investigate whether ethanolic extract of Hedyotis corymbosa L. (EEH) performs anticancer properties by inhibiting migration and metastasis on breast cancer cells. Cytotoxic evaluation by using MTT assay was carried out to determine EEH effect on 4T1 breast cancer cells, meanwhile to investigate the treatment of EEH in migration and metastasis inhibitory effect, scratch wound healing assay and gelatin zymography were conducted in this study. The data showed that EEH possessed cytotoxic activity with IC50 value of 400 μg/mL. Interestingly, migration inhibitory effect was shown up to 42 hours and the activity of MMP-9 was also decreased after the treatment with EEH. According to these findings, we suggest that Hedyotis corymbosa L. promotes another anticancer properties by inhibiting migration and metastasis towards breast cancer cells.Keywords : Hedyotis corymbosa L., cytotoxicity, migration, metastatic, 4T1 breast cancer cell
The Safety of Areca Seed Ethanolic Extract as Potential Chemopreventive Agent is Proven by Acute Toxicity Test
Full text linkAreca (Areca catechu L.) seeds ethanolic extract (AE) exhibits antiproliferative activity and induces apoptosis on T47D and MCF-7 cells. This study aimed to verify AE safety using acute toxicity test to support its development as chemopreventive agent. Male Sprague Dawley Rat (Rattus norvegicus) age 8 weeks divided into five groups, one group of control treated with 0.5% CMC-Na only and four groups for treatment. Single dose in oral administration was done to test animal with various dose of AE starts from lowest dose to highest dose expected toxic to all of test animal (0.1; 0.72; 5.36 and 10 gram/kgBW). Observation was done during 24 hours and continued for 14 days. The observation criteria were toxic symptoms, appearance and mechanism of toxic effect and pathology of vital organ. Histopathology analysis of some vital organs was done with Haematoxyllin&Eosin (H&E) staining. Toxic effect did not appear either on treatment groups or control group. Treatment of single dose of areca ethanolic extract, even in highest dose, did not cause the death of the animals. Therefore, observation extended to 14 days and terminated by necroption of the animals. All of groups did not show histopathological alterations in microscopic observation. Category of the potential toxicity of AE is practically non-toxic, ie 10 g/kgBW. The result shows the safety of areca seed ethanolic extract which is important for its development as chemopreventive agent.Keywords: Areca catechu, acute toxicity, ra
PENINGKATAN SENSITIVITAS SEL KANKER KOLON WiDr TERHADAP 5-FLUOROURASIL OLEH FRAKSI ETIL ASETAT KAYU SECANG (Caesalpinia sappan L.) MELALUI INDUKSI APOPTOSIS
No full textContinuous administration of chemotherapy in cancer cells could decrease its
sensitivity to chemotherapeutic agent. Strategy to overcome this problem is cochemotherapy
with chemoprevention agent which has synergist effect with
chemotherapeutic agent to eradicate cancer cells. On this research, we studied ethyl
acetate fraction of Caesalpinia sappan L. (EFC) as co-chemotherapeutic agent. EFC
was characterized using thin layer chromatography (TLC). Cytotoxic effect of EFC
was examined using MTT assay, apoptosis detection using double staining assay, and
we observed expression of cleaved PARP as apoptotic protein marker using
immunocytochemistry. Potency of EFC and 5-Fluorouracil (5-FU) against WiDr cell
lines was identified through IC50 value. Effect of combination 5-FU and EFC was
determined form combination index (CI) as parameter of synergist effect from this
combination. Apoptosis induction was determined through result from double
staining assay and expression of cleaved PARP.
Visual TLC profile of EFC with system consist of n-heksan, kloroform,
metanol, asam asetat glasial (1:7:2:1) as mobile phase and silika F254 as stationary
phase showed EFC contain brazilein as major compound with hRf 81. EFC could
inhibit WiDr cancel cells growth through decrease of cells viability and morphology
changing. IC50 value of EFC is 11 μg/mL in dose dependent manner. 5-FU as
chemotherapeutic agent for colon cancer showed cytotoxic effect with IC50 558 μM.
Combination of EFC and 5-FU showed synergist effect with CI value 0,3 at dose ½
IC50 of EFC and ½ IC50 of 5-FU. Synergist effect of this combination is predicted
through apoptosis induction that showed in double staining assay result. Apoptosis
mechanism was showed through decrease expression of cleaved PARP
Pentagamavunon-0 (PGV-0) Enhance Cytotoxic Effect of Doxorubicin through Increasing of Apoptosis, Senescence and ROS Level on Triple Negative Breast Cancer 4T1
Full text linkTNBC, one of the sub type of breast cancers was widely known with high tumorigenic and poor prognosis than others. The development of combination agent (co-chemotherapy) with doxorubicin for chemotherapy of TNBC were carried out to decrease doxorubicin side effect and resistance in cancer. This present study aims to explore the co-chemotherapeutic properties of PGV-0 and investigate induction of doxorubicin on apoptosis, senescence and ROS against TNBC. 4T1 Cell line were used as a TNBC in vitro model. Cytotoxic measurement was performed using MTT assay resulting in IC50 values of 52 μM. Meanwhile, the combination of doxorubicin and PGV-0 showed synergistic effect which decreased cell viability of 4T1 better than single treatment of doxorubicin. Apoptosis analysis was performed using annexin V/PI assay indicated that the combination treatment of PGV-0 and doxorubicin increased apoptosis evidence. Senescence detection was carried out using senescence-associated-β galactosidase (SA-β-gal) assay. The results showed that a single treatment of PGV-0 induced cellular senescence and increased senescence cells in combination treatment. Moreover, DCFDA staining showed that PGV-0 increased ROS level at single treatment, whereas combination treatment increased ROS intracellular compared to the positive control of doxorubicin. Based on these results, PGV-0 has potential as a co-chemotherapeutic candidate on TNBC.Keyword: 4T1, PGV-0, Co-chemotherapy, Cytotoxic, Senescence, Apoptosis, RO
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