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All Journal Indonesian Journal of Pharmaceutical Science and Technology Universa Medicina The Avicenna Medical Journal Journal of Science and Technology Research for Pharmacy Indonesian Journal of Cancer International Journal of Cell and Biomedical Science Indonesian Journal of Biomedicine and Clinical Sciences Biosaintifika: Journal of Biology & Biology Education Indonesian Journal of Medical and Pharmaceutical Science
Ibrahim, Sugeng
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Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Chemistry Computer Science & IT Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience Public Health

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Alpinia galanga Extract Inhibits MCF-7/HER2+ Cells by Inducing Apoptosis Ibrahim, Sugeng
Journal of Science and Technology Research for Pharmacy Vol 1 No 2 (2021)
Publisher : Universitas Negeri Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15294/jstrp.v1i2.51512

Abstract

Background: Cancer is a disease caused by abnormal growth of body tissue cells. Cancer treatment strategy by induce apoptosis and inhibit proliferation. Aim: This research aims to examine the anticancer effect of Alpinia galanga extract on MCF-7/HER2+ breast cancer cells. Method: The MTT Assay cytotoxic test was carried out to determine the growth inhibitory activity. Apoptotic assay to determine the activity of compounds in apoptosis, as well as through a structural approach utilizing various virtual platforms to monitor its activity. Result: Based on the MTT assay Alpinia galanga extract possessed cytotoxic effect in dose-dependent manner with IC50 value of 330.79 μg/mL. The extract induces apoptosis of MCF-7 cells up to 25.56%. Conclusion: It can be concluded that Alpinia galanga extract demonstrated cytotoxic activity toward MCF-7/HER2+ breast through apoptosis induction. This extract had an opportunity to be developed as a potential anticancer agent to overcome breast cancer diseases.
Synergistic Cytotoxicity of 5-Fluorouracil and Epigallocatechin-3-Gallate on Colorectal Cancer Stem Cell Ibrahim, Sugeng; Riwanto, Ignatius; Suharti, Catharina; Putra, Agung; Budijitno, Selamat
Indonesian Journal of Cancer Vol 18, No 2 (2024): June
Publisher : http://dharmais.co.id/

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v18i2.1211

Abstract

Background: Colorectal cancer stem cells (CR-CSCs) derived from the HCT-116 cell line established human colon carcinoma cell line, validated with CD44+/CD133+. The study investigates the synergistic effects of combining epigallocatechin gallate (EGCG) with 5-fluorouracil (5-FU) on CR-CSCs through comprehensive cytotoxicity assessments, aiming to enhance therapeutic outcomes. EGCG is a polyphenol with anti-cancer activity in green tea. Previous studies have reported that the anti-cancer activity of EGCG involves inhibition of proliferation and induction of apoptosis thereby reducing recurrence by as much as 51.6% in patients with colorectal adenoma after polypectomy. The significance lies in optimizing treatment strategies by understanding the potential synergies between conventional chemotherapeutic agents and natural compounds. Given 5-FU's status as a cornerstone in CR-CSCs chemotherapy and EGCG's emergence as a promising natural compound, the study delves into their individual and combined cytotoxicity profiles. Methods: The single and combination assay aimed to determine the cytotoxicity of EGCG and 5-FU, including establishing the half inhibitory concentration (IC50) and combination index (CI) values. CR-CSCs colonies were disassociated, counted, and cultured in 96-well plates. Test solutions of varying concentrations were applied, and subsequent steps involved incubation, media removal, washing, MTT reagent addition, and absorbance measurement. Results: The single cytotoxicity tests established individual IC50 values, revealing 141.26 µM for 5-FU and 464.56 µM for EGCG. Subsequent combination cytotoxicity tests demonstrated a synergistic effect at specific doses, indicated by CI values below 1. Conclusions: These findings highlight the potential for increased cytotoxicity against CR-CSCs when treated with the combination of 5-FU and EGCG.
Therapeutic Potential of Secretome Hypoxia Mesenchymal Stem Cells: Downregulation of TNF-α and HIF-2α in Metabolic Syndrome-Induced Inflammation in Wistar Rats Dewi, Alisia Martha; Trisnasi, Setyo; Putra, Agung; Chodijah , Chodijah; Sarosa, Hadi; Mulyani, Sri Priyantini; Amalina, Nur Dina; Ibrahim, Sugeng
Biosaintifika: Journal of Biology & Biology Education Vol. 16 No. 2 (2024): August 2024
Publisher : Universitas Negeri Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15294/biosaintifika.v16i2.6613

Abstract

Background: Metabolic syndrome (MetS) has become a global health challenge with several associated issues, such as obesity, insulin resistance, dyslipidemia, and hypertension. Important proteins such as Tumor Necrosis Factor-alpha (TNF-α) and Hypoxia Inducible Factor-2 alpha (HIF-2α) regulate the inflammatory process by inducing the expression of pro-inflammatory proteins. Secretome Hypoxia Mesenchymal Stem Cells (SH-MSCs) are immunomodulatory, anti-inflammatory, and angiogenic stimulators, which can regulate various inflammatory diseases, including MetS. Objective: This study aims to determine the effect of administering SH-MSCSs on the expression of the TNF-α and Hypoxia Inducible Factor (HIF)-2α genes in the male Wistar rat model with Metabolic Syndrome. Method: This research is an experimental study with a Post-test Only Control Group Design, using a total of 24 male Wistar rats divided into four groups: T1 (Healthy control), T2 (MetS + NaCl), T3 (MetS + administration of SH-MSCs dose 150 uL), and T4 (MetS + administration of SH-MSCs dose 300 uL). SH-MSCSs were administered intraperitoneally four times over 14 days. Adipose tissue TNF-α and HIF-2α gene expression were measured on day 15 using qRT-PCR. Results: TNF-α and HIF-2α gene expression was significantly lower in T3 and T4, compared with the MetS control group (T2). Conclusion: Administration of SH-MSCs was able to reduce the expression of the Tumor Necrosis Factor (TNF-α) and Hypoxia Inducible Factor (HIF)-2α genes in fatty tissue in the male Wistar rat model with Metabolic Syndrome.
Cooperative Impact of Curcuma longa and Phyllanthus niruri Extracts on Cytotoxicity in HCT-116 Cells Ibrahim, Sugeng; Hidayah, Nurul; Rifai, Fauziah Novita Putri; Ginanto, Dede
International Journal of Cell and Biomedical Science Vol 2 No 5 (2023)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v2i5.36

Abstract

Background: The combination of herbal extracts has the potential to enhance cytotoxic effects against cancer cells. This study explores the combined cytotoxic effects of Curcuma longa and Phyllanthus niruri extracts on HCT-116 colorectal cancer cells. Objective: To assess the cytotoxic effects of Curcuma longa and Phyllanthus niruri extracts when used in combination and to determine the most effective ratio for inhibiting HCT-116 cell growth. Methods: HCT-116 cells were treated for 24 hours with varying concentrations of Curcuma longa and Phyllanthus niruri extracts based on the IC50 values of each extract administered individually. The concentrations for Phyllanthus niruri were 164 µg/mL (one part), 82 µg/mL (half part), and 41 µg/mL (quarter part), while for Curcuma longa the concentrations were 47 µg/mL (one part), 24 µg/mL (half part), and 12 µg/mL (quarter part). Cytotoxicity was assessed using the MTT assay. Results: The combination of Phyllanthus niruri and Curcuma longa extracts demonstrated varied cytotoxic effects. The most effective combination was identified as Phyllanthus niruri to Curcuma longa ratio of 1:0.25, resulting in a 13.5% cell viability rate. Interaction studies using the Chou-Talalay method indicated that the combination index (CI) revealed the most synergistic effect at a ratio of 0.25:0.50. Conclusion: The study identifies that the combination of Phyllanthus niruri and Curcuma longa extracts exhibits synergistic cytotoxic effects on HCT-116 cells, with the optimal combination showing significant inhibition of cell growth. These findings support further investigation into the synergistic potential of these extracts for colorectal cancer therapy.
Anti-inflammation effect of Apium graveolens Extract against lead-acetate-induced brain injury in rats Sulistyo, Sona; Sarosa, Hadi; Sumarawati, Titiek; Putra, Agung; Chodidjah, Chodidjah; Amalina, Nur Dina; Ibrahim, Sugeng
International Journal of Cell and Biomedical Science Vol 2 No 6 (2023)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v2i6.41

Abstract

Purpose: The current study investigated the protective potential of Apium graveolens extract (APE) against lead-induced brain injury in rats by exploring anti-inflammatory and antiapoptotic mechanism. Methods: Twenty male Wistar rats were randomly allocated into four groups (n=5). The control group was orally administrated with distillate water. The second group received lead acetate 200mg/kg body weight orally for 14 days, the third group were orally administered lead acetate 200 mg lead acetate/kg body weight and vitamin E 50IU/kg body weight for 14 days. The fourth group was administrated with leas acetate like second group and APE 300mg/kg body weight for 14 days. The TNF-a levels and caspase-3 expression was analyses under ELISA and flow cytometry assay, respectively. Results: The phytochemical analysis of APE indicated the presence of alkaloids, flavonoids, tannins, saponins, and steroids. Leads acetate increased the serum levels of TNF-α and caspase-3 expression, as well as altering the brain tissue architecture. Conclusion: In conclusion, the presence of APE inhibited the lead acetate toxicity by inhibition of TNF-α proinflammation protein and caspase-3 proapoptosis protein.
The Effect of Celery Extract on Caspase-3 and TNF-α Gene Expression in Lead Poisoning-Induced Renal Injury in Rats Purwaningsih, Hesti; Sumarawati, Titiek; Chodidjah, Chodidjah; Putra, Agung; Priyantini, Sri; Fasitasari, Minidian; Ibrahim, Sugeng; Amalina, Nur Dina
International Journal of Cell and Biomedical Science Vol 2 No 6 (2023)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v2i6.42

Abstract

Background To determine the effect of Apium graveolens L (Celery) extract in the TNF-α and caspase-3 gene expression on the lead poisoning-induced renal injury rats’ model. Methods This study is experimental research with post test only control group design. Twenty male Wistar rats were randomly allocated into four groups (n=5). The control group was orally administrated with distillate water. The second group received lead acetate 200mg/kg body weight orally for 14 days, the third group were orally administered lead acetate 200 mg lead acetate/kg body weight and vitamin E 50IU/kg body weight for 14 days. The fourth group was administrated with leas acetate like second group and celery extract 300mg/kg body weight for 14 days. The TNF-a and caspase-3 gene expression was analyses under qRT-PCR. Results The phytochemical analysis of APE indicated the presence of alkaloids, flavonoids, tannins, saponins, and steroids. Leads acetate increased the TNF-α (3.87±0.09) and caspase-3 (7.95±0.23) gene expression. The celery extract was significantly decrease in the TNF-α (3.13±0.34) and caspase-3 (2.48±1.23) gene expression. Conclusion: In conclusion, the presence of celery extract inhibited the renal injury-induced lead acetate toxicity by inhibition of TNF-α proinflammation protein and caspase-3 proapoptosis protein
Effect of Typhonium flagelliforme Extract on the Viability of Colorectal Cancer Cells HCT-116 Sadikin, Nadya Audina N; Nazar, M. Ariq; Ibrahim, Sugeng
International Journal of Cell and Biomedical Science Vol 3 No 7 (2024)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v3i7.46

Abstract

Background: Colorectal cancer (CRC) remains a significant global health challenge, with rising incidence rates, particularly among younger individuals [1]. Conventional treatments, including chemotherapy and radiation, often cause severe side effects, necessitating the exploration of alternative therapeutic options. Typhonium flagelliforme, a medicinal plant widely used in traditional medicine, has been investigated for its cytotoxic potential against HCT-116 colorectal cancer cells. Objective: This study assessed the cytotoxic effects of T. flagelliforme extract on HCT-116 colorectal cancer cells using the MTT assay. Methods: The cytotoxicity of Typhonium flagelliforme (T. flagelliforme ) extract on HCT-116 colorectal cancer cells was assessed using the MTT assay after 24 hours of treatment with different concentrations (20–100 µg/mL). Results: The findings revealed a dose-dependent reduction in cell viability, with an IC₅₀ value of 73.47 µg/mL, indicating moderate cytotoxic activity. Higher extract concentrations (100–60 µg/mL) significantly decreased cell viability, while the lowest concentration (20 µg/mL) showed a paradoxical increase, possibly due to a hormesis effect. Conclusion: The findings revealed a dose-dependent reduction in cell viability, with an IC₅₀ value of 73.47 µg/mL, indicating moderate cytotoxic activity.
Hypoxia-preconditioned mesenchymal stem cells attenuate proinflammatory cytokines in collagen loss animal model Fristiani, Yeni; Putra, Agung; Sumarawati, Titiek; Setiawan, Eko; Ibrahim, Sugeng; Pramukarso, Dodik Tugasworo Pramukarso
Universa Medicina Vol. 44 No. 2 (2025)
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2025.v44.131-140

Abstract

Background Repeated ultraviolet-B (UVB) exposure induces significant collagen degradation, primarily through overproduction of reactive oxygen species, which subsequently drives an inflammatory cascade. Hypoxia-preconditioned mesenchymal stem cells (H-MSCs) constitute a promising therapeutic approach to counteract collagen loss by modulating inflammatory pathways. This study aimed to evaluate the potential of H-MSCs in regulating NF-κB p65 and IL-1β expression in a collagen loss rat model, highlighting their therapeutic efficacy. Methods Twenty-five healthy male Wistar rats were randomly assigned to five groups: K1 (healthy controls), K2 (collagen loss), K3 (collagen loss + hyaluronic acid), K4 (collagen loss + 2.5 × 10⁵ H-MSCs), and K5 (collagen loss + 5 × 10⁵ H-MSCs). Collagen loss was induced by UVB radiation (peak wavelength: 302 nm) for 2 weeks. mRNA expression of NF-κB p65 was quantified by qRT-PCR, while IL-1β levels were assessed using ELISA. The rats were maintained for 14 days before being sacrificed, to allow the H-MSCs to exert their therapeutic effects. Data analysis was by One-way ANOVA with Tukey’s post-hoc test. Results The administration of H-MSCs significantly reduced IL-1β levels in groups K4 (633.14±63.76 pg/mL) and K5 (520.80±123.82 pg/mL) compared to group K2 (931.93±205.80 pg/mL) (p<0.05), with group K5 showing the most substantial reduction. Moreover, H-MSC injection in groups K4 and K5 effectively reduced NF-κB p65 expression levels (1.13±0.50 a.u. and 0.72±0.22 a.u., respectively), compared to group K2 (2.47±0.50 a.u.) (p<0.05), with group K5 providing optimum inhibition. Conclusion This study demonstrated that H-MSCs effectively attenuate UVB-induced inflammation and modulate key inflammatory pathways.
Effector Cytokine Profiles of Ex Vivo Expanded CTLs in Colorectal Cancer HCT-116 Cells Co-Culture Models Ibrahim, Sugeng; Putra, Agung; Hidayah, Nurul; Cahyani, Dini
Indonesian Journal of Medical and Pharmaceutical Science Vol. 4 No. 2 (2025)
Publisher : Sultan Agung Islamic University of Semarang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30659/ijmps.v4i2.450

Abstract

Background: Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, with limited benefit from conventional therapies in advanced disease. Cytotoxic T lymphocytes (CTLs, CD8⁺ T cells) are critical mediators of anti-tumor immunity, primarily through direct cytotoxicity and cytokine secretion. However, the dual roles of CTL-derived cytokines, particularly interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), in CRC progression remain incompletely understood. This study aims to analyze the cytokine profile (IFN-γ, TNF-α, and IL-6) in a CTL–CRC cell direct co-culture model. Methods: CD8⁺ T cells were isolated from peripheral blood mononuclear cells (PBMCs) of CRC patients using magnetic negative selection and activated for 5 days with anti-CD3/CD28 beads and IL-2. Purity and viability were assessed by flow cytometry and morphology. Activated CTLs were co-cultured with the HCT116 CRC cell line at effector-to-target (E:T) ratios of 1:1, 5:1, and 10:1 under direct contact for 48 h. Supernatants were collected and cytokine levels (IFN-γ, TNF-α, and IL-6) were quantified using validated sandwich ELISA kits. Results: Direct co-culture with HCT116 cells significantly increased cytokine secretion in an E:T ratio-dependent manner. IFN-γ secretion rose from 3044.6±120 pg/mL at 1:1 to 4882.1±198 pg/mL at 5:1, plateauing thereafter. TNF-α levels remained relatively constant (628.6±67 pg/mL at 1:1 vs. 674.0±91 pg/mL at 10:1). IL-6, nearly undetectable at 1:1 (0.4±0.1 pg/mL), increased dose-dependently to 5.1±0.9 pg/mL at 10:1. Conclusion: Ex vivo expanded CTLs from CRC patients exhibit a distinct cytokine secretion profile characterized by robust IFN-γ release, stable TNF-α production, and a dose-dependent increase in IL-6 across different effector-to-target ratios.
Effects of Extracellular pH Modulation on HIF-1α, c-Myc, and FOXO1 Expression in Colorectal Cancer Cells Ibrahim, Sugeng; Putri Rifai, Fauziah Novita; Arda, Adzani Gaisani
International Journal of Cell and Biomedical Science Vol 4 No 10 (2025)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v4i10.67

Abstract

Background: The tumor microenvironment (TME) of colorectal cancer (CRC) is characterized by an inverted pH gradient, with acidic extracellular and alkaline intracellular conditions that promote tumor progression and metabolic reprogramming. This altered pH landscape regulates key transcriptional drivers of glycolysis and proliferation, including hypoxia-inducible factor-1 alpha (HIF-1α), c-Myc, and the tumor suppressor Forkhead Box Protein O1 (FOXO1). Understanding how extracellular pH influences these regulators may provide new insights for pH-targeted cancer therapy. Methods: Human colorectal carcinoma HCT116 cells were cultured for 24 hours under six extracellular pH conditions (5.5–9.2). The expression of HIF-1α, c-Myc, and FOXO1 was quantified using quantitative real-time polymerase chain reaction (qPCR), and relative fold changes were analyzed by the 2^-ΔΔCt method. Results: Acidic conditions (pH 5.5–6.7) markedly upregulated HIF-1α and c-Myc while strongly suppressing FOXO1 expression. Conversely, mild alkalinity (pH 8.4) reversed this pattern, reducing HIF-1α and c-Myc while restoring FOXO1 expression, suggesting a transcriptional shift from glycolytic to oxidative metabolism. At higher alkalinity (pH 9.2), the expression of all three genes declined, indicating a threshold beyond which excessive pH elevation becomes detrimental to cellular regulation. Conclusion: Extracellular pH critically modulates metabolic gene expression in CRC cells. Acidic conditions activate glycolytic and oncogenic pathways via HIF-1α and c-Myc, while mild alkalinity suppresses these signals and reinstates tumor-suppressive FOXO1 activity. Controlled alkalinization of the TME may therefore represent a promising adjunctive approach to disrupt tumor metabolism and limit cancer progression.
Co-Authors Agung Putra Amalina, Nur Dina Arda, Adzani Gaisani Cahyani, Dini Catharina Suharti Chodidjah Chodidjah Chodijah , Chodijah Dewi, Alisia Martha Eko Setiawan Eko Setiawan Fahreza, Rakha Fikriya Novita Sari Fristiani, Yeni Ginanto, Dede Hadi Sarosa Haitamy, Mohammad Nurrizki Ignatius Riwanto, Ignatius Khan, Ahmed Faheem Minidian Fasitasari Mohammad Ariq Nazar Muhar, Adi Muradi Nugraha, Dendi Krisna Nurul Hidayah NURUL HIDAYAH Pramukarso, Dodik Tugasworo Pramukarso Purwaningsih, Hesti Rifai, Fauziah Novita Putri Sadikin, Nadya Audina N Selamat Budijitno Setyo Trisnadi Sri Priyantini Sri Priyantini Mulyani Sulistyo, Sona Taskworo, Dodik Titiek Sumarawati Trisnasi, Setyo Utami, Wulan Dyah