Rohmad Yudi Utomo
Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada

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Ethanolic Extract of Papaya (Carica papaya) Leaf Exhibits Estrogenic Effects In Vivo and In Silico Sugiyanto, Raisatun Nisa; Khamsita, Rahmi; Lambertus, Marvin; Utomo, Rohmad Yudi; Susidarti, Ratna Asmah
Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Research Gateway

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Abstract

The menopause women have the low level of estrogen in the body. The lack of estrogen changes physiological function in womens body that affects in health condition. Carica papaya L. leaf contains flavonoid quercetin which exhibits estrogenic effect. The aim of this study is to determine the estrogenic effect of papaya leaves extract (PLE) in vivo, and in silico. Papaya leaves were extracted by ethanol 70% maceration. The in silico study were done by molecular docking between quersetin and Estrogen Receptor (ERα and ERß) to obtain the docking score. Based on this study, docking score of quercetin was almost similar to the native ligand of ER. The in vivo study was done as follow: 36 female rats Sprague Dawley divided into six groups. The groups are shame-ovariectomized (S-OVX), control ovariextomized (OVX), CMC-Na control (OVX+CMC-Na), positive control (OVX+Estradiol), and the PLE treatment groups dose 750 mg/kgBW (OVX+750mg/kgBW) and dose 1000 mg/kgBW (OVX+1000 mg/kgBW). Administrations of PLE were done in three weeks orally, while estradiol was administrated intraperitonially. The mammae and uterine were sliced for analysis. Based on the study, the treatment of PLE increased the number of mammae lobules and uterine weight as well as estrogen does. In summary, PLE can be developed as a source of phytoestrogens.Keywords: Carica papaya L., phytoestrogen, estrogen receptor, mammae lobule, uterine
SYNTHESIS AND CYTOTOXIC ACTIVITY OF 2,5-BIS(4-BORONIC ACID)BENZYLIDINE CYCLOPENTANONE ON HER2 OVEREXPRESSED-CANCER CELLS Utomo, Rohmad Yudi; Putri, Herwandhani; Pudjono, Pudjono; Susidarti, Ratna Asmah; Jenie, Riris Istighfari; Meiyanto, Edy
INDONESIAN JOURNAL OF PHARMACY Vol 28 No 2, 2017
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (949.546 KB) | DOI: 10.14499/indonesianjpharm28iss2pp74

Abstract

Development of chemotherapeutic agent and boron carrying pharmaceutical based on HER2 specific targeted is important due to its role in enhancing cancer progression. The purpose of this study is to synthesize curcumin analogue, namely Pentagamaboron-0 (PGB-0) or 2,5-bis(4-boronic acid)benzylidine cyclopentanone, and to explore the cytotoxic activity on HER2 overexpressed-cancer cells. MCF-7/HER2 was used as a model of HER2 overexpressed-cancer cells and NIH3T3 as normal cells. PGB-0 bound to ATP binding site of HER2 and EGFR based on molecular docking study. PGB-0 was synthesized resulting in 33% yield and was confirmed by IR, 1HNMR, 13CNMR and Mass spectroscopy. Based on MTT assay PGB-0 decreased cells viability on MCF-7/HER2 cells with IC50 value of 270 µM but performed no effect on NIH3T3 cells. Cell cycle analysis revealed that PGB-0 increased sub-G1 accumulation. PGB-0 decreased HER2 expression in a dose-dependent manner. We conclude that the new compound PGB-0 inhibits cell growth through cell death induction and decreased HER2 expression. Thus, PGB-0 is potential to be developed as a chemotherapeutic agent and boron carrying pharmaceutical targeted on the HER2 receptor.
Anti-metastatic effect of curcumin analog pentagamaboronon-0-fructose (PGB-0-F) against 4T1 breast cancer cells Ertanto, Yogi; Utomo, Rohmad Yudi; Jenie, Riris Istighfari; Susidarti, Ratna Asmah; Meiyanto, Edy
Indonesian Journal of Biotechnology Vol 23, No 2 (2018): In Press
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijbiotech.36431

Abstract

Development of chemotherapeutic agent and boron carrying pharmaceutical based on triple negative breast cancer is important due to its metastatic progression. Metastases are often more dangerous than the primary tumor and they are responsible for 90% of all cancer deaths.  The purpose of this study is to explore the anti-metastatic activities of the PGB-0 complex with fructose (PGB-0-F) against 4T1 breast cancer cells. Scratch wound healing assay was performed to determine migration inhibition ability of PGB-0-F, while MMP-9 expression were analysed by gelatin zymography.  The testing of anti-migration activity showed that PGB-0-F inhibited  in 4T1 cells, whereas in gelatin zymography assay showed the suppression of MMP-9 expression. PGB-0-F inhibited closure on 4T1 metastatic breast cancer cells line compared to control. PGB-0-F decreased MMP-9 expression level compared to control. Based these results, PGB-0-F has a potency to be developed as chemotherapeutic agent especially as anti-metastatic agent
Cytotoxic and Apoptotic-inducing Effect of Fraction Containing Brazilein from Caesalpinia sappan L. and Cisplatin on T47D Cell Lines Tirtanirmala, Prisnu; Novarina, Annisa; Utomo, Rohmad Yudi; Sugiyanto, Raisatun Nisa; Jenie, Riris Istighfari; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 6, No 3 (2015)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (689.242 KB) | DOI: 10.14499/indonesianjcanchemoprev6iss3pp89-96

Abstract

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
Anti-metastatic Activity of Curcumin Analog Pentagamaboronon-0-Sorbitol Against HER2-overexpressed MCF-7 Breast Cancer Cells Qodria, Lailatul; Hairunisa, Indah; Utomo, Rohmad Yudi; Hermawan, Adam; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 9, No 3 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1706.584 KB) | DOI: 10.14499/indonesianjcanchemoprev9iss3pp118-125

Abstract

Breast cancer with Human Epidermal Growth Factor Receptor (HER)2 overexpression increases tumor progession and lead to metastasis, which is primarily cause of mortality in breast cancer. Pentagamaboronon-0 Sorbitol (PGB-0-So) is an aquoeous formulation of curcumin analog, PGB-0, with sorbitol. This compound has been developed as an anti-cancer chemotherapeutic agent and a boron carrying pharmaceutical for boron neutron capture therapy (BNCT). The aims of this study are to investigate antimetastatic activities of PGB-0-So against HER2-overexpressed MCF-7 breast cancer (MCF-7/HER2) cells. The MTT cytotoxicity assay of PGB-0-So exhibited cytotoxic effect with an IC50 value of 35 μM. The testing of anti-migration activity using the scratch wound healing assay demonstrated that PGB-0-So inhibited the closure of the wound on MCF-7/HER2 cells compare to the control. Furthermore, PGB-0-So was able to suppress matrix metalloproteinase (MMP)-9 activities, based on the gelatin zymography assay. In conclusion, PGB-0-So has potency to be developed as an anti-cancer agent against metastatic breast cancer.Keywords : PGB-0-So, anti-metastatsis, cell migration, MMP-9, MCF-7/HER2
Curcumin Analog Pentagamaboronon-0-Sorbitol Inhibits Cell Migration Activity of Triple Negative Breast Cancer Cell Line Ramadani, Ratna Dwi; Utomo, Rohmad Yudi; Hermawan, Adam; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 9, No 3 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1109.864 KB) | DOI: 10.14499/indonesianjcanchemoprev9iss3pp126-133

Abstract

Mortality in cancer is primarily due to failure of metastasis prevention. One strategy to target the cancerous cell is Boron Neutron Captured Therapy which showed high affinity toward cancer cells and reported to have anti-proliferative as well as antimetastatic activities. Cancer Chemoprevention Research Center Faculty of Pharmacy Universitas Gadjah Mada, has developed boron-containing substance namely pentagamaboronon-0 (PGB-0) which is known to exhibit anticancer activity towards breast cancer cell. The purposes of this research are focused to explore the anti-migratory activities of PGB-0-So against triple negative breast cancer cell. The MTT cytotoxicity assay of PGB-0-So against 4T1 breast cancer cell line were found to exert potential effect in dose-dependent manner with IC50 values of 39 μM. The study of cell migration inhibition using in vitro wound healing assays and gelatin zymography on highly metastasis breast cancer cell line 4T1, following the treatment of sub IC50 doses of PGB-0-So complex slightly inhibited cell migration through the inhibition of matrix metalloproteinase-9 expression. These findings suggest that PGB-0-So is potential as an anticancer agent.Keywords : curcumin analogue, PGB-0-So, 4T1 Cells, migration, MMP-9 
Pentagamaboronon-0 Fructose Inhibited Migration and Overexpression of Matrix Metalloproteinases 9 on MCF-7/HER2 Breast Cancer Cells Hairunisa, Indah; Utomo, Rohmad Yudi; Ertanto, Yogi; Jenie, Riris Istighfari; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 9, No 3 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1255.442 KB) | DOI: 10.14499/indonesianjcanchemoprev9iss3pp134-142

Abstract

The incidence of Breast Cancer Metastasis (MBC) can be categorized in stage IV as well as being the leading cause of death in cases of breast cancer. MBC prognosis is known to be weak, frequent recurrent, and MBC patients have only a survival rate of about 5 years. One of the proteins that causes breast cancer metastasis is Human Epidermal Growth Factor 2 (HER2). Pentagamaboron-0 (PGB-0), a newly curcumin analogue performed cytotoxic effect on HER2-positive breast cancer cells but it is practically water-insoluble. The aims of this study are to determine anti-metastatic activity of a more soluble form of PGB-0 namely PGB-0 fructose complex (PGB-0-F) toward HER2 positive cancer (MCF-7/HER2) cells. PGB-0-F was obtained from Cancer Chemoprevention Research Centre Faculty of Pharmacy Universitas Gadjah Mada. Based on scratch wound healing assay result, PGB-0-F inhibited cell migration especially in combination with doxorubicin at the concentration 15 μM. Under gelatin zymography assay, PGB-0-F in combination with doxorubicin decreased Matrix Metalloproteinases 9 (MMP-9) expression compare to the doxorubicin. Hence, PGB-0-F has a potency to be developed as anti-metastatic agent on HER2 overexpression breast cancer.Keywords : HER2, MCF-7/HER2, PGB-0-F, Metastasis
Enhancement of Cytotoxicity and Apoptosis Induction of Doxorubicin by Brazilein Containing Fraction of Secang (Caesalpinia sappan L.) on T47D Cells Utomo, Rohmad Yudi; Novarina, Annisa; Tirtanirmala, Prisnu; Kastian, Ria Fajarwati; Jenie, Riris Istighfari
Indonesian Journal of Cancer Chemoprevention Vol 9, No 1 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (451.872 KB) | DOI: 10.14499/indonesianjcanchemoprev9iss1pp32-40

Abstract

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
Ethanolic Extract of Papaya (Carica papaya) Leaf Exhibits Estrogenic Effects In Vivo and In Silico Sugiyanto, Raisatun Nisa; Khamsita, Rahmi; Lambertus, Marvin; Utomo, Rohmad Yudi; Susidarti, Ratna Asmah
Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (933.343 KB) | DOI: 10.14499/indonesianjcanchemoprev3iss2pp384-390

Abstract

The menopause women have the low level of estrogen in the body. The lack of estrogen changes physiological function in women’s body that affects in health condition. Carica papaya L. leaf contains flavonoid quercetin which exhibits estrogenic effect. The aim of this study is to determine the estrogenic effect of papaya leaves extract (PLE) in vivo, and in silico. Papaya leaves were extracted by ethanol 70% maceration. The in silico study were done by molecular docking between quersetin and Estrogen Receptor (ERα and ERβ) to obtain the docking score. Based on this study, docking score of quercetin was almost similar to the native ligand of ER. The in vivo study was done as follow: 36 female rats Sprague Dawley divided into six groups.  The groups are shame-ovariectomized (S-OVX), control ovariectomized (OVX), CMC-Na control (OVX+CMC-Na), positive control (OVX+Estradiol), and the PLE treatment groups dose 750 mg/kgBW (OVX+750mg/kgBW) and dose 1000 mg/kgBW (OVX+1000 mg/kgBW). Administrations of PLE were done in three weeks orally, while estradiol was administrated intraperitonially. The mammae and uterine were sliced for analysis. Based on the study, the treatment of PLE increased the number of mammae lobules and uterine weight as well as estrogen does.  In summary, PLE can be developed as a source of phytoestrogens.Keywords: Carica papaya L., phytoestrogen, estrogen receptor, mammae lobule, uterine
Antigenotoxicity Activity of Papaya (Carica papaya L.) Leaf Ethanolic Extract on Swiss Mice Induced Cyclophosphamide through Mammalian In Vivo Micronucleus Test Shabrina, Bani Adlina; Juansa, Juang; Putri, Nindya Budiana; Utomo, Rohmad Yudi; Murwanti, Retno
Indonesian Journal of Cancer Chemoprevention Vol 7, No 1 (2016)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (582.221 KB) | DOI: 10.14499/indonesianjcanchemoprev7iss1pp31-37

Abstract

Cyclophosphamide (CPA) is an effective chemotherapeutic agent, but has side effect, causing DNA damage (genotoxic). Papaya leaf (Carica papaya L.) is known has flavonoid compound, quercetin. Quercetin is known has DNA protecting effect (antigenotoxic effect) by metabolism modulation. Thus, the aim of this research is to investigate the antigenotoxic effect of ethanolic extract of papaya (Carica papaya L.) leaf (EEPL) on CPA induced mice. The antigenotoxic effect was evaluated by mammalian in vivo micronucleus test. EEPL was orally administered as single treatment at dose 1000 mg/kgBW and in combination with CPA 50 mg/kgBW at dose 250 mg/kgBW; 500 mg/kgBW; and 1000 mg/kgBW. Molecular docking using PLANTS on CYP 3A4 was performed to explore the antigenotoxic effect mechanism. The three different combination dose of EEPL with CPA significantly (P<0.05) decreased the amount of micronucleated polychromatic erytrhocyte (MNPCE)/1000 polychromatic erythrocyte (PCE) and also increased % PCE/(PCE+normochromatic erythrocyte (NCE)), compared with single dose of CPA. Nevertheless, the antigenotoxic effect wasn’t significant compared with each combination dose. The docking score result showed quercetin (-82,41) has more potent interaction to CYP 3A4 than cyclophosphamide (-70,16) and both of them has similar active site at amino acid residue Ile 369 and Thr 309. The results obtained indicated that EEPL at dose 250 mg/KgBB is the optimal dose as antigenotoxic agent by interaction between quercetin with CYP 3A4 based on molecular docking.Keywords: antigenotoxic, Carica papaya L., MNPCE, in vivo