Kanker payudara merupakan kanker terbanyak di Indonesia dengan angka mortalitas yang tinggi. Kandungan acetogenin, alkaloid, tannin, dan flavonoid pada daun sirsak dipercaya dapat menghambat pertumbuhan sel kanker. Tujuan: Mengetahui pengaruh ekstrak daun sirsak terhadap viabilitas cell line kanker payudara T47D secara in vitro. Metode: Ini merupakan penelitian eksperimental dengan metode MTT menggunakan cell line T47D yang dibagi menjadi 8 kelompok perlakuan konsentrasi ekstrak daun sirsak dan tiga variasi masa inkubasi serta pengulangan sebanyak empat kali. Pemeriksaan dibaca menggunakan xMark microplate reader dan selanjutnya ditentukan konsentrasi ekstrak yang dapat menghambat 50% viabilitas sel. Hasil: Ada penurunan viabilitas sel seiring dengan peningkatan konsentrasi yang diberikan pada ketiga masa inkubasi. Konsentrasi ekstrak yang dapat menghambat 50% viabilitas sel pada masa inkubasi 24 jam 569,8μg/ml, 48 jam 431,6 μg/ml, dan 72 jam 94,26 μg/ml. Simpulan: Ekstrak daun sirsak berpengaruh terhadap viabilitas cell line kanker payudara T47D dan dapat menghambat 50% viabilitas sel pada konsentrasi 94,26 μg/ml pada masa inkubasi 72 jam yang berpotensi sebagai antikanker.

BACKGROUND: The expression of a gene is a process that conveys information of genes to synthesise gene product is functional. Alterations of the molecular biology in breast cancer are very complex because of many factors play a role in the tumorigenesis. RhoC is a prometastases gene. The PI3K gene is crucial in the regulation of multiple cellular functions, including cell growth, proliferation, metabolism and angiogenesis.AIM: This study aims to compare of RhoC and PI3K gene expression on the breast cancer tissue and benign tumour tissue.MATERIAL AND METHODS: Expression of the RhoC and PI3K genes was carried out with qPCR. The absolute quantification method was using breast cancer tissue. As a comparison, benign tumours (FATs) tissue was carried out. The standard curves were obtained from cloning target genes, which were inserted into the gGEMT-easy vector from E. coli. The gene expression data was carried out by t-test to see the mean difference between the expression of breast cancer tissue and benign tumours (FATs) with a value of p ≤ 0.005 in RhoC and PI3K gene expression. And the relationship between expressions was done by Pearson correlation test.RESULTS: The results showed that it was found that PI3K gene expression on breast cancer tissue was higher than the number in a benign tumour (fibroadenoma mammae) as an endogenous control. And also, the expression of RhoC is much lower on breast cancer tissue compared with a benign tumour. CONCLUSION: This study concluded that expression of RhoC affects the expression of PI3K so that the thing this is what causes the proliferation and began to provide support aggressive cancer cells in the breast.

Introduction: Breast cancer remains a prevalent global malignancy and necessitates a treatment regimen, which is often accompanied by substantial side effects. To address this challenge, alternative therapies with fewer adverse effects are urgently needed. Amomum cardamomum has displayed promising anticancer potential. This study aimed to investigate the impact of A. cardamomum seed on T47D breast cancer cell viability and the ability to induce apoptosis, utilizing in silico and in vitro approaches. Methods: The samples were extracted utilizing the maceration method using ethanol 96% solvent. In addition, the bioactive constituents were identified through phytochemicals and GC/MS analysis. Cell viability was assessed through MTT assay at various concentrations with 24 and 48-hour incubation periods and compared with the control cells. Apoptosis patterns were visualized by Immunofluorescence assay and analyzed utilizing ImageJ software. In silico analyses included three distinct tests, namely pharmacokinetics analysis (ADMET), bioactivity prediction (PASS), and molecular docking. Results: The A. cardamomum seed extract inhibited the growth of the cells with an IC50 value of 97.28 μg/mL in 48 hours of the incubation period. Immunofluorescence assay exhibited that the extract induced apoptosis in over 50% of T47D cells. In silico approaches identified bicyclogermacrene, Germacrene-D, and δ-cadinene as potential JAK3, BRAF v600e, and MMP9 protein inhibitors. These compounds exhibited stronger binding affinities to critical amino acids than control ligands. Conclusion: This research presents compelling evidence that the A. cardamomum extract has anticancer activity against breast cancer by preventing growth and inducing apoptosis.

Atherosclerosis is a leading cardiovascular disease characterized by the buildup of plaques within arterial walls. The aim of this study was to investigate the potential of peptides derived from Lytechinus variegatus spines as novel therapeutic agents for atherosclerosis using an in silico approach. Key proteins involved in atherosclerosis were selected as target proteins: vascular endothelial growth factor receptor (VEGFR), protein kinase B (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 8 (MAPK8), and endothelin-1 (ET-1). Comprehensive analysis involving ligand and protein preparation, toxicity, and allergenicity assessments, absorption, distribution, metabolism and excretion (ADME) predictions, and molecular docking were conducted to evaluate the safety, pharmacokinetic properties, binding affinity (kcal/mol), root mean square deviation (RMSD) (Å), as well as a 2D and 3D visualization. Toxicity predictions revealed that peptide 9 was non-toxic and non-allergenic, with a lethal dose 50 (LD50) of 3,000 mg/kg, indicating its safety. Peptide 9 demonstrated the most promising results, effectively inhibiting VEGFR2 (-10,90 kcal/mol), AKT1 (-10,56 kcal/mol), EGFR (-9,82 kcal/mol), MAPK8 (-9,64 kcal/mol), and ET-1 (-11,41 kcal/mol) with strong binding affinities and specificity. These interactions suggested that peptide 9 from Lytechinus variegatus spines may serve as a competitive multitarget inhibitor, offering potential multitarget therapeutic activity against atherosclerosis. Peptide 9 also had high water solubility and did not affect the concentration or excretion of other drugs or compounds, minimizing the risk of drug-drug interactions.

Context: Triple-negative breast cancer (TNBC) is a breast malignancy with a high degree of heterogeneity. Currently, low treatment efficacy remains a challenge in dealing with TNBC. Arbacia lixula has the potential to become a new therapeutic agent in TNBC. Aims: To analyze the toxicity, allergenicity, and potential of A. lixula coelomic fluid peptides as agents that inhibit cell cycle progression and angiogenesis in TNBC cancer cells in silico. Methods: Eight A. lixula coelomic fluid peptides were modeled with UCSF Chimera software. All peptides were screened using the ToxinPred and AllerTop webserver to predict their toxicity and allergenicity. The 3D structures of GSK3B, CDK2, and VEGFR2 proteins were taken from the PDBJ database. Molecular docking was carried out using the MOE application. Results: Peptides 2, 4, 6, and 7 were non-toxic and non-allergen. Peptide 4 has the strongest binding affinity value for binding the ATP binding pocket proteins GSK3β (-11.57 kcal/mol) and VEGFR2 (-11.18 kcal/mol). Peptide 4 interacts similarly with ATP, as a native ligand, on the amino acid residues of GSK3B and VEGFR2. Peptide 1 has a binding affinity value of -10.16 kcal/mol, much stronger than ATP in the CDK2 protein, and forms the same two interactions as ATP at the amino acid residues Asp86 and Lys129. Conclusions: Peptide 1 and peptide 4 of A. lixula coelomic fluid have great potential as anti-TNBC by inhibiting the activity of proteins that play a crucial role in cell cycle progression and TNBC angiogenesis via an ATP competitive inhibitor mechanism through an in silico approach.

Latar Belakang: Kanker payudara merupakan jenis kanker dengan angka kejadiannya menempati posisi pertama terbanyak di Indonesia dibandingkan dengan jenis kanker lain. Daun sirsak yang mengandung acetogenin memiliki efek sitotoksik terhadap sel kanker payudara T47D. Objektif: Penelitian ini bertujuan untuk mengetahui pengaruh ekstrak daun sirsak terhadap level ekspresi gen p53 sel kanker payudara T47D secara in vitro. Metode: Penelitian ini merupakan penelitian eksperimental dengan metode kuantifikasi relatif real time PCR menggunakan cell line T47D diinkubasi selama 72 jam yang dibagi menjadi 2 kelompok sampel, yaitu perlakuan dan kontrol. Kelompok perlakuan diberikan larutan uji ekstrak etanol daun sirsak dengan konsentrasi IC50 = 94,26 µg/ml. Hasil: Hasil nilai Cq dari gen target dan referensi dianalisis dengan menggunakan uji Mann Whitney dan rumus livak. Hasil penelitian didapatkan perbedaan yang bermakna antara kelompok perlakuan dan kontrol dengan nilai p = 0,003 (p < 0,05). Analisis dengan rumus livak menunjukkan adanya peningkatan ekspresi gen p53 sel kanker payudara T47D yang diberi perlakuan, yaitu 2,8015 kali lipat lebih tinggi dari sel kelompok kontrol. Kesimpulan: Ekstrak daun sirsak efektif dapat meningkatkan ekspresi gen p53 pada cell line T47D dan terdapat perbedaan yang bermakna dari nilai Cq gen p53 sel kelompok perlakuan dan kontrol.