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Arief Nurrochmad
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281
Biochemistry, Genetics & Molecular Biology Public Health

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Curcumin Enhances Antimigration of Pentagamavunon-1 by Suppressing MMP-2 and MMP-9 Expression in Triple-Negative (4T1) and Luminal A (T47D) Breast Cancer Cells Desty Restia Rahmawati; Edy Meiyanto; Riris Istighfari Jenie; Arief Nurrochmad
The Indonesian Biomedical Journal Vol 17, No 1 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i1.3431

Abstract

BACKGROUND: Breast cancer remains the leading cause of cancer death worldwide. Migration and invasion of cancer cells are still crucial stages in the metastasis process, highlighting the urgent need for treatments that target both proliferation and metastatic progression. Curcumin and its synthetic analogue, pentagamavunon (PGV)-1, exhibit antiproliferative effects in breast cancer cells. However, the effects of combining curcumin and PGV-1 on cancer cell migration have not yet been explored. Therefore, this study was conducted to examine the antimigratory effects of curcumin and PGV-1 combination on 4T1 and T47D breast cancer cells.METHODS: Cytotoxicity effects of curcumin and PGV-1 were examined using an MTT assay to determine their effects on 4T1 and T47D cell viability. The antimigration activity was assessed using a scratch wound healing assay by measuring the closure of artificially created wounds on monolayer cells. Expression of matrix metalloproteinases (MMPs) that play a crucial role in cancer cell migration was analyzed using gelatin zymography to measure their enzymatic activities.RESULTS: The IC50 of PGV-1 and curcumin were 4.88 μM and 37.62 μM in 4T1 cells and 3.16 μM and 23.15 μM in T47D cells, respectively. Furthermore, combination of PGV-1 and curcumin effectively inhibited 4T1 and T47D cell migration. PGV-1 (0.5–2 μM) demonstrated superior antimigratory activity compared to curcumin (5–20 μM) by suppressing MMP-2 and MMP-9 expression in both cell lines. Significantly, curcumin was shown to synergistically enhance the antimigratory effects of PGV-1, leading to a further decrease in MMP-2 and MMP-9 expression. CONCLUSION: The combination of PGV-1 and curcumin may provide a promising antimigratory agent, potentially leading to enhanced antimetastatic strategies and more efficacious treatments for triple-negative and luminal breast cancer patients.KEYWORDS: antimigration, curcumin, luminal breast cancer, MMP-2, MMP-9, pentagamavunon-1, triple-negative breast cancer
Pentagamavunon-1 Enhances the Anticancer Effects of Doxorubicin on Triple-Negative Breast Cancer Cells in Monolayers and 3D Cancer Spheroid Models Desty Restia Rahmawati; Retno Murwanti; Riris Istighfari Jenie; Arief Nurrochmad
The Indonesian Biomedical Journal Vol 17, No 3 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i3.3587

Abstract

BACKGROUND: The 4T1 cells, a triple-negative breast cancer (TNBC) cell line, exhibit high malignancy and metastatic potential. As a primary treatment for TNBC, doxorubicin has limitations, including drug resistance mechanisms and severe side effects such as cardiotoxicity. Pentagamavunone-1 (PGV-1) exhibits antiproliferative and antimetastatic effects, induces prometaphase arrest, triggers cell senescence, and enhances reactive oxygen species (ROS) modulation, which may help overcome doxorubicin resistance. The selective cytotoxicity of PGV-1 against cancer cells suggests that it has a role in reducing systemic toxicity. Therefore, in this study, the anticancer effects of doxorubicin combined with PGV-1 was investigated.METHODS: Monolayer/2D and spheroid/3D models of 4T1 cells were used to assess the effects of PGV-1, doxorubicin, and their combination. MTT assay was used to evaluate the cytotoxicity, colony formation assay was used to measure persistent antiproliferative effects, and spheroid volume analysis was performed to assessed tumor growth inhibition. Senescence-associated beta-galactosidase (SA-β-gal) assay determined cellular senescence.RESULTS: The combination of PGV-1 and doxorubicin significantly enhanced cytotoxicity, with IC50 values of 0.57 µM and 4.88 µM, respectively (p=0.000). A strong synergistic effect was observed, leading to persistent suppression of cancer cell proliferation and an 80% reduction in colony formation (p=0.007). In the 3D spheroid model, combination treatment significantly reduced spheroid volume (p=0.002) more effectively than monotherapy, indicating superior growth inhibition and cytotoxicity. It also increased SA-β-gal, the senescence marker (p=0.010).CONCLUSION: The combination of PGV-1 and doxorubicin demonstrated potent anticancer effects in 4T1 monolayers and spheroid models by enhancing cytotoxicity and inducing cellular senescence. This combination confirmed its potential as a more effective therapeutic strategy.KEYWORDS: 3D spheroid, 4T1 TNBC cell, doxorubicin, pentagamavunon-1, PGV-1, senescence
Immunomodulatory Effect of Dioscorea esculenta L. on NF-κB, TLR-4, TNF-α, and IL-10 Expressions in LPS-stimulated RAW 264.7 Mouse Macrophages Ika Puspitaningrum; Muthi Ikawati; Nanang Fakhrudin; Arief Nurrochmad
The Indonesian Biomedical Journal Vol 17, No 3 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i3.3630

Abstract

BACKGROUND: Gene expressions of toll-like receptor 4 (TLR)-4, nuclear factor-kappaB (NF-κB), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 are known to have roles in the inflammatory process and affect the regulation of the immune system. A preliminary study showed that Dioscorea esculenta L. tuber has immunomodulatory activity against macrophage phagocytosis activity and lymphocyte proliferation. However, the immunomodulatory activity of aqueous extract (AE), polysaccharide fraction (PF), and non-polysaccharide fraction (NPF) of D. esculenta L. tubers on these gene expressions have not been elucidated well. Therefore, this study was performed to determine its immunomodulatory activity by utilizing RAW 264.7 cell culture induced by lipopolysaccharide (LPS).METHODS: RAW 264.7 cells were stimulated with LPS at a concentration of 1 µg/mL for 30 minutes before incubation with non-toxic concentrations of AE, PF, NPF, positive control, and inulin at 25 and 50 µg/mL. TNF-α, IL-10, TLR-4, NF-κB, and β-actin expressions were evaluated using reverse transcription-polymerase chain reaction (RT-PCR) and were normalized with β-actin as an internal control. Triplicate experiments were performed throughout this study.RESULTS: Treatment with 25 µg/mL NPF significantly decreased the expression of NF-κB, TLR-4, and TNF-α (p<0.05). In contrast, treatment of 25 and 50 µg/mL PF significantly decreased the NF-κB expression (p<0.05). Moreover, only treatment with 50 µg/mL AE exhibited a significant increase in IL-10 expression (p<0.05).CONCLUSION: Treatment with D. esculenta L. tuber stimulated macrophage RAW 264.7 cells via NF-κB, TLR-4, TNF-α, and IL-10 expressions. NPF at 25 µg/mL has stronger immunomodulatory activity in reducing the expression of genes involved in the inflammatory process that plays a role in regulating the immune system.KEYWORDS: Dioscorea esculenta L., Immunomodulator, IL-10, NF-κB, TLR-4, TNF-α, RAW 264.7 cell
Co-Authors Desty Restia Rahmawati Edy Meiyanto Ika Puspitaningrum Muthi Ikawati Nanang Fakhrudin Retno Murwanti Riris Istighfari Jenie