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All Journal Indonesian Journal of Cancer Chemoprevention Indonesian Journal of Biotechnology
Rohmad Yudi Utomo
Cancer Chemoprevention Research Center Faculty Of Pharmacy Universitas Gadjah Mada
Biochemistry, Genetics & Molecular Biology Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology

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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

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (4.399 KB)

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
Anti-metastatic effect of curcumin analog pentagamaboronon-0-fructose (PGB-0-F) against 4T1 breast cancer cells Yogi Ertanto; Rohmad Yudi Utomo; Riris Istighfari Jenie; Ratna Asmah Susidarti; Edy Meiyanto
Indonesian Journal of Biotechnology Vol 23, No 2 (2018)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (8.602 KB) | DOI: 10.22146/ijbiotech.36431

Abstract

Development of a 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 was to explore the anti-metastatic activities of the PGB-0 complex with fructose (PGB-0-F) against 4T1 breast cancer cells. A scratch wound healing assay was carried out to determine the migration inhibition ability of PGB-0-F, while MMP-9 expression was analysed using gelatin zymography. The testing of anti-migration activity showed that PGB-0-F inhibited in 4T1 cells, whereas the gelatin zymography assay revealed a suppression of MMP-9 expression. PGB-0-F inhibited closure on 4T1 metastatic breast cancer cells line compared with the control. PGB-0-F decreased the MMP-9 expression level compared with the control. Based on these results, PGB-0-F has the potential to be developed as a chemotherapeutic agent, and especially as an anti-metastatic agent.
Cytotoxic and Apoptotic-inducing Effect of Fraction Containing Brazilein from Caesalpinia sappan L. and Cisplatin on T47D Cell Lines Prisnu Tirtanirmala; Annisa Novarina; Rohmad Yudi Utomo; Raisatun Nisa Sugiyanto; Riris Istighfari Jenie; Edy Meiyanto
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 | 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 Lailatul Qodria; Indah Hairunisa; Rohmad Yudi Utomo; Adam Hermawan; Edy Meiyanto
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 | 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 Ratna Dwi Ramadani; Rohmad Yudi Utomo; Adam Hermawan; Edy Meiyanto
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 | 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 Indah Hairunisa; Rohmad Yudi Utomo; Yogi Ertanto; Riris Istighfari Jenie; Edy Meiyanto
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 | 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
Ethanolic Extract of Papaya (Carica papaya) Leaf Exhibits Estrogenic Effects In Vivo and In Silico Raisatun Nisa Sugiyanto; Rahmi Khamsita; Marvin Lambertus; Rohmad Yudi Utomo; Ratna Asmah Susidarti
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 | 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
Pentagamaboronon-0-Sorbitol Induces Apoptosis through Elevation of Reactive Oxygen Species in Triple Negative Breast Cancer Cells Ratna Dwi Ramadani; Rohmad Yudi Utomo; Adam Hermawan; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 12, No 1 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev12iss1pp46-56

Abstract

Breast cancer is the most common type of cancer causing mortality for women due to metastasis. More than 50% of breast cancer patients are suffered lung metastases. One strategy to target the cancerous cell is Boron Neutron Captured Therapy (BNCT) which showed high affinity toward cancer cells and reported to have anti-proliferative as well as anti-metastatic activities. Pentagamaboronon-0 (PGB-0) is a curcumin analogue substance which had reported to exert anticancer activities against Her-2 expressing as well as triple negative breast cancer cells. Despite its great potency as BNCT agent candidate, this compound also exerted several anticancer properties. Complex formation of this substance with sorbitol was achieved to improve the solubility and maximize compound’s delivery to the target cells. This study aimed to investigate the ability of Pentagamaboronon-0-Sorbitol (PGB-0-So) to modulate cell cycle and induce apoptosis especially through the mechanisms of reactive oxygen species (ROS) modulation. The 3-(4,5-dimethylthiazzol-2yl)-2,5-diphenyltetrazolium (MTT) cytotoxicity assay of PGB-0-So against 4T1 breast cancer cell line were found to exert potential effect in dose-dependent manner with lethal concentration (IC50) values of 39 μM. The cytotoxicity of PGB-0-So complex was found to be increased considerably compared with that of PGB-0. Cell cycle modulation identified using propidium iodide (PI) staining showed cell accumulation in S phase following treatment with PGB-0-So. Apoptosis induction assay analyzed using flowcytometer with Annexin V and PI staining on its IC50 dose was found to induce programmed cell death (apoptosis). The sub-IC50 treatment of this compound was also improved the cellular ROS level which also took role in apoptosis induction. These findings suggest that PGB-0-So is potential as an anticancer agent.Keywords: Curcumin analogue, PGB-0-So, Anticancer, 4T1 cell line, ROS modulation.
Antigenotoxicity Activity of Papaya (Carica papaya L.) Leaf Ethanolic Extract on Swiss Mice Induced Cyclophosphamide through Mammalian In Vivo Micronucleus Test Bani Adlina Shabrina; Juang Juansa; Nindya Budiana Putri; Rohmad Yudi Utomo; Retno Murwanti
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 | 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
Anti‐proliferative effects of pentagamaboronon‐0‐sorbitol on HER2‐overexpressing breast cancer cells Lailatul Qodria; Rohmad Yudi Utomo; Adam Hermawan; Edy Meiyanto
Indonesian Journal of Biotechnology Vol 27, No 2 (2022)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijbiotech.67549

Abstract

HER2‐positive breast cancer is an aggressive form of the disease that is associated with poor prognosis and chemo‐resistance. As such, investigation continues into the development of a new HER2‐targeted drug for breast cancer. This study investigated the anti‐proliferative activities of pentagamaboronon‐0‐sorbitol (PGB‐0‐So) in HER2‐overexpressing breast cancer (MCF‐7/HER2) cells. The cytotoxicity of PGB‐0‐So was assessed via MTT assay. Flow cytometry with propidium iodide and annexin‐V‐FITC staining was conducted to investigate the mechanism of PGB‐0‐So in inhibiting the proliferation of MCF‐7/HER2 cells. Finally, FACS analysis with 2′,7′–dichlorofluorescin diacetate staining was performed to examine intracellular ROS production. PGB‐0‐So exerted cytotoxicity towards MCF‐7/HER2 breast cancer cells with an IC50 value of 36 μM. PGB‐0‐So induced S‐phase arrest and apoptosis in MCF‐7/HER2 cells. Moreover, PGB‐0‐So could increase intracellular ROS production in MCF‐7/HER2 cells. PGB‐0‐So exerted anti‐proliferative activity towards MCF‐7/HER2 cells. This compound may be developed as a chemotherapeutic agent against HER2‐overexpressing breast cancer.
Co-Authors Adam Hermawan Annisa Novarina Bani Adlina Shabrina Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Indah Hairunisa Indah Hairunisa Jenie, Riris Istighfari Juang Juansa Lailatul Qodria Lailatul Qodria Marvin Lambertus Marvin Lambertus Nindya Budiana Putri Prisnu Tirtanirmala Rahmi Khamsita Rahmi Khamsita Raisatun Nisa Sugiyanto Raisatun Nisa Sugiyanto Ratna Asmah Susidarti Ratna Asmah Susidarti Ratna Dwi Ramadani Ratna Dwi Ramadani Retno Murwanti Riris Istighfari Jenie Riris Istighfari Jenie Yogi Ertanto Yogi Ertanto