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Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47D Rifai, Fauziah Novita Putri; Hanifa, Mila; Zulfin, Ummi Maryam; Ikawati, Muthi; Meiyanto, Edy
Journal of Tropical Biodiversity and Biotechnology Vol 9, No 1 (2024): March
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/jtbb.88238

Abstract

Pentagamavunone-1 (PGV-1), a curcumin analog, is a promising anticancer candidate for several cancers that have been proven in vitro and in vivo. However, the efficacy of PGV-1 against breast cancer is subject to improvement to achieve a more suitable application. Here we propose hesperitin, a citrus flavonoid, to increase the anticancer potency of PGV-1 in luminal breast cancer cells. We use the T47D cell as the model to investigate the effect of co-administration of PGV-1 and hesperitin on cell cycle block, apoptosis modulation, and senescence phenomena. PGV-1 and hesperitin showed strong and weak cytotoxicity with an IC50 value of 2 µM and 100 µM, respectively. The co-treatment of PGV-1 and hesperitin resulted in strong synergistic effects with combination index (CI) value of ≤ 0.2. This combination caused apoptosis in correlation with cell cycle disruption in G2/M phase at 48 h. In particular, PGV-1 and hesperitin combination increased the incidence of cellular senescence significantly higher than the single treatment. Despite its senescence potentiation, hesperitin did not induce senescence in normal cells. Taken together, hesperitin may increase the anticancer potency of PGV-1 by modulating cell cycle arrest and apoptosis via the senescence mechanism. 
Integrative Bioinformatics Reveals the Lactate Dehydrogenase B (LDHB) Significance in Colon Adenocarcinoma Wulandari, Febri; Hanifa, Mila
Molecular and Cellular Biomedical Sciences Vol 7, No 2 (2023)
Publisher : Cell and BioPharmaceutical Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21705/mcbs.v7i2.346

Abstract

Background: Lactate dehydrogenase B (LDHB), a typical oxidoreductase for converting lactate to pyruvate in the glycolysis process, takes a complex function in the progression of cancer cells. Even so, the profile of LDHB relevance in colon adenocarcinoma (COAD) remains ambiguous. Hence this study analyzed the expression and co-expression profile of LDHB, and its immune correlation in COAD.Materials and method: The mRNA expression and co-expression of LDHB in COAD were retrieved from UALCAN. The immune infiltration levels of LDHB from B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in COAD were assessed using the TIMER database. For assessing gene ontology and the KEGG pathway, DAVID v6.8 was utilized. The protein-protein interaction of LDHB-correlated genes was analyzed using STRINGDB and Cytoscape.Results: Significantly high expression of LDHB in COAD was spotted in several sample types and associated with a poor overall survival rate. Further, LDHB corresponded to the level of CD4+, macrophages, and myeloid-derived suppressor cell (MDSC) immune infiltrating cells. The co-expression of LDHB was associated with several essential genes for cell cycle progression.Conclusion: The findings of this study indicate an upcoming involvement of LDHB in COAD tumorigenesis and prognosis. Additionally, this study highlights the immune correlation of LDHB in COAD as preliminary data in developing diagnosis and treatment with a novel immune checkpoint in COAD.Keywords: lactate dehydrogenase, colon adenocarcinoma, expression, survival, immune
Network Pharmacology and In Vitro Validation of Brazilin as a Potential Apoptosis-Inducing Agent in HBV-Related Hepatocellular Carcinoma Hanifa, Mila; Utomo, Rohmad Yudi; Jenie, Riris Istighfari
Indonesian Journal of Cancer Chemoprevention Vol 15, No 3 (2024)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev15iss3pp210-223

Abstract

Hepatitis B virus (HBV) reactivation-related hepatocellular carcinoma (HCC) presents a significant threat due to its potential to cause liver failure and mortality. Consequently, the discovery of novel treatments that offer anticancer efficacy and liver protection is urgently needed. Brazilin, a natural compound, has previously been reported to possess cytotoxic and liver-protective properties. This research aimed to investigate the potency of brazilin in suppressing the growth of HCC cells through in silico and in vitro approaches. Hep3B cells, which harbor integrated HBV DNA, were selected as the HCC model, with PGV- 1 utilized as a positive control. The in silico study used network pharmacology to predict brazilin’s potential gene targets. Cytotoxicity was evaluated using the CCK-8 assay, and apoptosis detection was carried out using Annexin V/PI staining followed by flow cytometry. The analysis predicted that brazilin targets key genes such as SRC, EGFR, AKT1, GRB2, IGF1, ESR1, STAT1, MMP9, JAK2, and PPARG involved in cancer proliferation and metastasis. Proteins such as SRC, GRB2, and MMP9 are overexpressed in TP53-mutated HCC and linked to low survival. Brazilin showed moderate cytotoxicity with an IC50 value of 17 μM at 72 h and significantly induced apoptosis in Hep3B cells. These findings suggest that brazilin is a promising apoptosis-inducing agent for HBV-related HCC.Keywords: brazilin, Hep3B cell lines, network pharmacology, cytotoxic, apoptosis.