Papers by febri wulandari
Research Journal of Pharmacy and Technology
Triple-negative breast cancer (TNBC) remains as the deadliest cancer type due to the lack of trea... more Triple-negative breast cancer (TNBC) remains as the deadliest cancer type due to the lack of treatment options. Hence, several attempts have been made to develop new anticancer for TNBC therapy. This study intended to challenge curcumin analog (CCA)-1.1, which is derived from pentagamavunone-1 structure, against the 4T1 cell line and TNBC cell model, covering the cytotoxic activity in correlation with cell cycle progression, apoptosis induction, reactive oxygen species (ROS) generation, and senescence evidence. The cell viability, cell cycle profile, apoptosis induction, intracellular ROS level, and senescence induction were determined in vitro using trypan blue exclusion, propidium iodide (PI) staining, Annexin-PI staining, dichlorofluorescein diacetate staining, and senescence-associated-β-gal method. CCA-1.1 showed cytotoxic activity on 4T1 cells, giving half maximal inhibitory concentration value of 3M, but was less toxic on non-cancerous 3T3-L1 cells. CCA-1.1 induced rapid cel...
Scientific Reports
The treatment of glioblastoma multiforme (GBM) is challenging owing to its localization in the br... more The treatment of glioblastoma multiforme (GBM) is challenging owing to its localization in the brain, the limited capacity of brain cells to repair, resistance to conventional therapy, and its aggressiveness. Curcumin has anticancer activity against aggressive cancers, such as leukemia, and GBM; however, its application is limited by its low solubility and bioavailability. Chemoprevention curcumin analog 1.1 (CCA-1.1), a curcumin analog, has better solubility and stability than those of curcumin. In this study, we explored potential targets of CCA-1.1 in GBM (PTCGs) by an integrated computational analysis and in vitro study. Predicted targets of CCA-1.1 obtained using various databases were subjected to comprehensive downstream analyses, including functional annotation, disease and drug association analyses, protein–protein interaction network analyses, analyses of genetic alterations, expression, and associations with survival and immune cell infiltration. Our integrative bioinform...
Journal of Advanced Pharmaceutical Technology & Research, 2022
Boronic acid-containing curcumin analog, pentagamaboronon-0 (PGB-0), acts as a potential boron-ca... more Boronic acid-containing curcumin analog, pentagamaboronon-0 (PGB-0), acts as a potential boron-carrier agent but has limited water solubility. Thus, a new compound (PGB-0-ol) with better chemical and pharmacological properties than PGB-0 has been synthesized. Molecular docking was performed using a molecular operating environment. Prediction of PGB-0-ol absorption, distribution, metabolism, and excretion (ADME) was performed using pkCSM software. PGB-0-ol was synthesized by adding NaBH4 to PGB-0 and stirring for 1 h. The crude PGB-0-ol was purified using preparative layer chromatography. Cell viability was evaluated using the trypan blue exclusion assay. In comparison to PGB-0 based on molecular docking study, PGB-0-ol could interact in with several cancer biomarkers, such as human epidermal growth factor2 epidermal growth factor receptor, IκB kinase, folate receptor-α, and integrin αvβ3. PGB-0-ol also showed an improved ADME profile because of its higher water solubility than PGB-0...
Iranian Journal of Pharmaceutical Research, 2022
Pentagamavunon-1 performs more potent anti-cancer effects than curcumin against various cancer ce... more Pentagamavunon-1 performs more potent anti-cancer effects than curcumin against various cancer cells, but it remains to be optimized. Piperine shows the activity as an enhancer of a therapeutic agent. This study expects to achieve higher effectiveness of PGV-1 on 4T1 breast cancer cells through co-treatment with piperine with exploring the effect of cytotoxicity, mitotic catastrophe, cellular senescence, and target proteins of PGV-1 and piperine on the regulation of mitosis in TNBC cells (4T1). The assays emphasize MTT assay, May Grünwald-Giemsa staining, SA-β-galactosidase assay, and bioinformatics analysis, respectively, to elicit the respected activities. The results revealed that PGV-1 performed a cytotoxic effect with an IC50 value of 9 µM while piperine showed a lower cytotoxic effect with an IC50 value of 800 µM on 4T1 cells 24 h treatment. However, the combination treatment of both showed a synergistic cytotoxic enhancement effect with an average CI value < 1. Furthermore, the combination of PGV-1 and piperine induced mitotic catastrophe and senescence better than the single treatment. Treatment of 1 µM of PGV-1 and 400 µM of piperine increased the percentage of senescent cells by 33%. Bioinformatics analysis revealed that PGV-1 and piperine target proteins play a role in mitotic regulation, namely CDK1, KIF11, AURKA, AURKB, and PLK1, to contribute to mitotic catastrophe. Therefore, piperine increases the effectiveness of PGV-1 to suppress 4T1 cells growth synergistically that may occur through mitotic catastrophe and senescence targeting on mitotic regulatory proteins.
Asian Pacific Journal of Cancer Prevention, 2022
This strain exhibits relatively higher resistance to standard chemotherapy, particularly anthracy... more This strain exhibits relatively higher resistance to standard chemotherapy, particularly anthracyclines and taxanes, especially in the metastatic stage (Wahba and El-Hadaad, 2015). Standard chemotherapy has a shorter response duration, a higher recurrence rate, and shorter patient survival (André and Zielinski, 2012). Existing chemotherapeutic agents have a number of drawbacks, including resistance, side effects, and insufficient efficacy
Pentagamavunone-1 and its newest derivatives, CCA-1.1, possess an outstanding cytotoxic activity ... more Pentagamavunone-1 and its newest derivatives, CCA-1.1, possess an outstanding cytotoxic activity against several cancer cell lines, especially colorectal cancer. We are continuing to explore the anti-colorectal cancer properties of PGV-1 and CCA-1.1 against DMH-induced colorectal cancer rats and expound the potential protein target in colorectal adenocarcinoma. We utilized DMH 60 mg/kg (subcutaneous injection once a week for 16 weeks) to induce colorectal cancer. PGV-1 and CCA-1.1 at 10 and 20 mg/kg (orally twice a week for 16 weeks) were co-administered with DMH. The WBC count increased in a single DMH group and was countered by co-administration of PGV-1 and CCA-1.1, but no significant differences in RBC. Single DMH treatment for 16 weeks resulted in 80% adenocarcinoma. In contrast, co-administration with PGV-1 and CCA-1.1 suppressed most of the carcinogenic characteristics and symptoms of the pre-malignancy condition. Furthermore, bioinformatics analysis showed that CCA-1.1 has m...
Advanced Pharmaceutical Bulletin, 2021
Purpose: This study aimed to challenge the anticancer potency of pentagamavunone-1 (PGV-1) and ob... more Purpose: This study aimed to challenge the anticancer potency of pentagamavunone-1 (PGV-1) and obtain a new compound (Chemoprevention-Curcumin Analog 1.1, CCA-1.1) withimproved chemical and pharmacological properties.Methods: CCA-1.1 was prepared by changing the ketone group of PGV-1 into a hydroxylgroup with NaBH4 as the reducing agent. The product was purified under preparative layerchromatography and confirmed with HPLC to show about 93% purity. It was tested for itssolubility, stability, and cytotoxic activities on several cancer cells. The structure of the productwas characterized using 1HNMR, 13C-NMR, FT-IR, and HR-mass spectroscopy.Results: Molecular docking analysis showed that CCA-1.1 performed similar or better interactionto NF-κB pathway-related signaling proteins (HER2, EGFR, IKK, ER-alpha, and ER-beta) andreactive oxygen species (ROS) metabolic enzymes (NQO1, NQO2, GSTP1, AKC1R1, andGLO1) compared with PGV-1, indicating that CCA-1.1 exhibits the same or better anticance...
Asian Pacific Journal of Cancer Prevention, 2021
Objective: We aim to enhance the effectiveness of curcumin analog PGV-1 through co-treatment with... more Objective: We aim to enhance the effectiveness of curcumin analog PGV-1 through co-treatment with diosmin, a citrus flavonoid, on 4T1 cells and evaluate the molecular targets underlying its effect on the cell cycle. Methods: Cytotoxic effects were performed by MTT assay against 4T1 cells. The May Grünwald-Giemsa staining was used to observe cell cycle arrest. The senescence was assayed with SA-ß-gal staining. Bioinformatic studies were utilized to discover protein targets of PGV-1 and diosmin on triple-negative breast cancer (TNBC) using SwissTargetPrediction, then exploration of protein targets was performed using the TCGA dataset via the UALCAN website. Kaplan-Meier was performed using GraphPad with data from the TCGA dataset via Oncoln. Using MOE 2010, we conducted the binding affinity between PGV-1 and diosmin to protein targets. Results: PGV-1 and diosmin showed cytotoxic effect with IC 50 values of 9 µM and 389 µM, respectively, and the combined cytotoxic assay exhibited a synergistic effect with a combination index (CI) of <1. PGV-arrested 4T1 cells in pro-metaphase and induced mitotic catastrophe, while the combination of diosmin with PGV-1 increased the number of mitotic catastrophes. The SA-ß-gal assay revealed that both compounds were capable of inducing senescence in 4T1 cells. Study bioinformatics and molecular docking showed that PGV-1 and diosmin target cell cycle regulatory proteins in TNBC, namely CDK1, KIF11, and AURKA. Thus, the combination of diosmin and PGV-1 modulating the cell cycle that causes senescence and catastrophic death of 4T1 cancer cells is related to the inhibition of these cell cycle proteins. Conclusion: Diosmin enhances the cytotoxic effect of PGV-1 synergistically on 4T1 cancer cells, which correlates to the increasing senescence and mitotic catastrophe. The synergistic effect of the co-treatment is likely to target AURKA, CDK1, and KIF11. The combination of PGV-1 and diosmin performs a potential as a combinatorial anticancer drug for TNBC.
The Indonesian Biomedical Journal, 2021
BACKGROUND: Colon cancer is still a crucial concern in the development of chemotherapeutic drugs ... more 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 ...
Scientia Pharmaceutica, 2021
Pentagamavunon-1 (PGV-1), a potential chemopreventive agent with a strong cytotoxic effect, modul... more Pentagamavunon-1 (PGV-1), a potential chemopreventive agent with a strong cytotoxic effect, modulates prometaphase arrest. Improvement to get higher effectiveness of PGV-1 is a new challenge. A previous study reported that the natural compound, galangin, has antiproliferative activity against cancer cells with a lower cytotoxicity effect. This study aims to develop a combinatorial treatment of PGV-1 and galangin as an anticancer agent with higher effectiveness than a single agent. In this study, 4T1, a TNBC model cell, was treated with a combination of PGV-1 and galangin. As a result, PGV-1 and galangin showed a cytotoxic effect with IC50 values of 8 and 120 µM, respectively. Combining those chemicals has a synergistic impact, as shown by the combination index (CI) value of 1. Staining with the May Grunwald-Giemsa reagent indicated mitotic catastrophe evidence, characterized by micronuclear and multinucleated morphology. Moreover, the senescence percentage was higher than the single...
Indonesian Journal of Pharmacy, 2020
An improved compound of pentagamavunone-1 (PGV-1), chemoprevention-curcumin analog 1.1 (CCA-1.1),... more An improved compound of pentagamavunone-1 (PGV-1), chemoprevention-curcumin analog 1.1 (CCA-1.1), has been synthesized and proven to have antiproliferative effects against breast cancer cells. This study is designed to investigate the potency of CCA-1.1 alone and in combination with doxorubicin (Dox) on T47D cells in comparison with that of PGV-1. We used the MTT assay to assess cytotoxic activity. Propidium iodide (PI), annexin-V–PI, and DCFDA staining were respectively used to determine cell cycle profiles, apoptosis, and intracellular reactive oxygen species (ROS) levels. Senescent cells were identified using the SA-b-galactosidase assay. Our results revealed that CCA-1.1 possesses cytotoxic effects similar to those of PGV-1 on T47D cells. Synergistic effects during co-treatment with Dox were also observed. CCA-1.1 arrested cell cycle progression at the G2/M phase and limited sub-G1 accumulation, which is correlated with apoptosis. CCA-1.1 alone and in combination with Dox increa...
Gene Reports, 2020
The chemoprevention-curcumin analog 1.1 (CCA-1.1) is a derivative of Pentagamavunone-1 (PGV-1) eq... more The chemoprevention-curcumin analog 1.1 (CCA-1.1) is a derivative of Pentagamavunone-1 (PGV-1) equipped with augmented chemical and physical properties. This study explores the potential therapeutic targets and pathways of CCA-1.1 for colon cancer treatment using bioinformatic studies. Gene mutations associated with colon cancer were retrieved from the cBioPortal public database. Target genes of CCA-1.1 were obtained from seven online databases. We then analyzed the gene ontology profiles, KEGG-related pathways, protein-protein interaction (PPI) networks, related diseases, and drug associations of the potential target genes. A total of 914 mutated genes and 812 predictive target genes of CCA-1.1 were aligned, resulting in 93 genes of matches genes mainly enriched in the pathways of cancer metabolism and EGFR tyrosine-kinase inhibitor resistance. The top 20 hub genes showed major involvement in colorectal cancer. Drug association analysis demonstrated that CCA-1.1 was mostly related to protein kinase inhibitors. Three genes, including TP53, MAPK1, and ERBB2, were revealed as noticeable target genes of CCA-1.1; these were involved in colon cancer-related pathways and had important prognostic value. Overall, the putative target genes of CCA-1.1, including TP53, MAPK1, and ERBB2, and related pathways identified in this study, suggest a possible mechanism of CCA-1.1 that could contribute to the anticolon cancer drug development. Considering the drug-target prediction databases (Daina et al., 2019; Yao et al., 2016), it will offer more information from which to obtain related predictive biomarkers and pathways in colon cancer and even to discover novel therapeutic markers with high prognostic significance. The drug of choice in colon cancer therapy is 5-Fluorouracil (5-FU),
Journal of Applied Pharmaceutical Science, 2021
The new Pentagamavunone-1 (PGV-1) derivative, chemoprevention-curcumin analog 1.1 (CCA-1.1), is d... more The new Pentagamavunone-1 (PGV-1) derivative, chemoprevention-curcumin analog 1.1 (CCA-1.1), is described as an improved physicochemical feature with similar cytotoxic activity on colon cancer cells and binding interaction to various cancer biomarkers. The current study explored the cytotoxic activity related to its ability to promote physiological changes in the WiDr colon cancer cell line. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess the cell viability of WiDr and NIH-3T3 cells on the treatment of CCA-1.1 and PGV-1. 2′,7′-dichlorofluorescein diacetate staining, propidium iodide staining, and annexin V-PI staining were conducted to examine reactive oxygen species (ROS) level, cell cycle profiles, and apoptosis, respectively. For more examination on morphological changes, the SA-β-gal staining was used to detect senescence occurrence. We retrieved a more significant cytotoxic effect on WiDr by CCA-1.1 than PGV-1 and no effect on NIH-3T3 fibroblast cells. Our compound stimulated the arrest of the cell cycle at the G2/M phase, apoptosis, ROS generation, and senescence at an equal level to PGV-1. Altogether, these data reinforce CCA-1.1 as a viable alternative to PGV-1, attributed to its improved physicochemical features that are beneficial in designing dosage formulations for medical purposes.
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Papers by febri wulandari