Edy Meiyanto
Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Farmako, Sekip Utara, Yogyakarta 55281

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Curcumin Analogs, PGV-1 and CCA-1.1 Exhibit Anti-migratory Effects and Suppress MMP9 Expression on WiDr Cells Febri Wulandari; Muthi' Ikawati; Mitsunori Kirihata; Jun-Ya Kato; Edy Meiyanto
The Indonesian Biomedical Journal Vol 13, No 3 (2021)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v13i3.1583

Abstract

BACKGROUND: Colon cancer is still a crucial concern in the development of chemotherapeutic drugs due to the drug resistance phenomenon and various side effects to patients. One of the newest compound that show anticancer activities against several cancer cells, Chemoprevention Curcumin Analog 1 (CCA-1.1), has increasingly been explored to overcome the limitation of conventional drugs.METHODS: We evaluated the anti-migratory effect of CCA-1.1 and Pentagamavunone-1 (PGV-1) by using WiDr colon cancer cells. The expression profiles of Tumor Protein 53 (TP53) and Matrix Metalloproteinase-9 (MMP9) in colon cancer were obtained from the UALCAN database. Survival outcomes of TP53 and MMP9 in colon cancer patients were analyzed using the Kaplan-Meier method. We used 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), scratch wound healing, and gelatin zymography assays to observe the cytotoxic effect, anti-migratory activity, and MMP9 expression, respectively, in CCA-1.1 or PGV-1-treated cells.RESULTS: Level of MMP9 was found significantly overexpressed in the primary tumor and metastasis nodal, while TP53 mutation sample types were observed and influenced the survival outcome in colon cancer patients. CCA-1.1 and PGV-1 exhibited strong cytotoxic activity after 24 and 48 h treatment against WiDr cells. The migration assay demonstrated that PGV-1 and CCA-1.1 at 1 mM inhibited cell migration up to 40% after 48 h in single and combination with doxorubicin. The MMP9 expression was significantly inhibited by 0.5 mM CCA-1.1.CONCLUSION: This study emphasizes that the anti-migratory effect of CCA-1.1 is better than PGV-1 via MMP9 suppression on WiDr. Thus, CCA-1.1 is prominent to be developed as an anti-metastatic agent.KEYWORDS: chemopreventive curcumin analog 1.1 (CCA-1.1), PGV-1, WiDr cells, anti-migration, MMP9
Curcumin Analogs PGV-1 and CCA-1.1 Induce Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells with Overexpressed MYCN Moordiani Moordiani; Dhania Novitasari; Ratna Asmah Susidarti; Muthi' Ikawati; Jun-ya Kato; Edy Meiyanto
The Indonesian Biomedical Journal Vol 15, No 2 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i2.2147

Abstract

BACKGROUND: Liver cancer is the third leading mortality in cancer. Curcumin shows effective anticancer potency against various cancer including liver cancer. The synthesized curcumin analog compounds Pentagamavunone-1 (PGV-1) and Chemoprevention Curcumin Analog-1.1 (CCA-1.1) have been well studied in breast, leukemia, and colon cancer cells with better potency than curcumin itself, yet their cytotoxic activities were not known in liver cancer cells. Thus, this study was conducted to elevate the anticancer effect of these curcumin analogs against hepatocellular carcinoma (HCC) cells in vitro, specifically in MYCN-expressing cells, based on its cellular physiology.METHODS: JHH-7 cells were used as the HCC cell model with high expression of MYCN. The viability of the cells was observed using trypan blue exclusion method while cell cycle profile and intracellular reactive oxygen species (ROS) levels were quantified by means of flow cytometry. Chromosomal staining with Hoechst was applied to determine the cell cycle arrest phase, whilst X-gal staining was used to assess the cellular senescence activity.RESULTS: The result of current study presented that the growth inhibitory activity of PGV-1 as well as CCA-1.1 in JHH-7 cells was associated with the cell cycle arrest and cellular senescence. Both curcumin analogs PGV-1 and CCA-1.1 ultimately induced mitotic arrest (p<0.001) better than curcumin. Moreover, PGV-1 and CCA-1.1 similarly increased the senescent cells that partly mediated through ROS elevation. The transcription level of MYCN was not altered upon treatment with curcumin and its analogs in JHH-7 cells, suggesting that molecular mechanism of the inhibitory effect was independent from MYCN signaling.CONCLUSION: Taken together, these observations revealed that both PGV-1 and CCA-1.1 potentially serve as multi-targeted curcumin-based compounds and lead to promising anti-hepatocellular cancer agents.KEYWORDS: Curcumin analogs, hepatocellular carcinoma, mitotic arrest, MYCN