Fadilah

In silico, in vitro and in vivo Tests of Ficus deltoidea Jack Leaves Extract as Inhibitor for Beta-Catenin Expression in Colon Carcinogenesis Model

Context: Ficus deltoidea Jack leaves extract as anticolorectal cancer. Aims: This study aims to analyze the potential of FD extract to be an anti-colon cancer by investigating the extract capability in reducing β-catenin expression and inhibiting colon cancer cells growth. Settings |and Design: The research was conducted in Medical Faculty Universitas Indonesia with experimental design. Methods and Material: FD ethanol extracts was tested in vitro, in silico and in vivo. In vitro test was conducted to human colon cell lines. In vivo test was conducted to Balb/c mice induced with 10 mg/kg azoxymethane (AOM) and dextran sodium sulfate 1% (DSS). The colonic tissue collected was the distal portion. β-catenin expressions in the cytoplasm and nuclei of the epithelial cells of the colon crypt were semi quantitatively assessed using the immunohistochemistry staining on ten visual fields with 400x magnification. Statistical analysis used: SPSS. Results: FD ethanol extracts inhibit the expression of β-catenin in the crypt ephitelial cells of mice colon induced with AOM/DSS. The extracts also inhibit the growth of human colon cancer (HCT 116) with IC50 value of 5.41 mg/mL. Phytochemical screening to the extracts gave three groups of compounds: alkaloid, flavonoid, and tannin. Water fraction is the best fraction. Based on in the results of in silico analysis with molecular docking, FD extract is believed to influence the expression of β-catenin, in which vitexin and isovitexin are the main candidate compounds to influence the expression of the protein. Conclusion: FD ethanol extract is potential to be an anti-colon cancer proven by the extract capability to reduce β-catenin expression.

In Silico Study and Cytotoxicity of the Synthesized Open-chain Analogues of Antimycin A3 Against HEP-2 Laryngeal Cancer Cells

Background: Laryngeal cancers affect one quarter of all head and neck cancers. Chemotherapy is a standard method in treatment laryngeal carcinoma. How-ever, cancer chemotherapy is often a failure due to the appearance of drug resistance. This fact suggests that the search for novel, safe, and more effective laryngeal cancer drugs are required. Antimycin A3 is a fit ligand of anti-apoptotic Bcl-2. While Bcl-2 is known to be over-expressed in laryngeal cancer cell, it is quite reasonable to expect an-timycin A3 and its analogue to induce apoptosis in those cells. Methods: With this viewpoint, we decided to conduct research that is aimed to evaluate cytotoxic activity of the synthesized open-chain analogues of antimycin A3 against HEP-2 laryngeal cancer cells, as well as to conduct in silico study of the analogues on receptor binding target Bcl-2 of laryngeal cancer. Results and Conclusion: Open-chain analogues of antimycin A3 were successfully syn-thesized in a good yield from Boc-L-Threonine by esterification, amidation, and Sharp-less asymmetric dihydroxylation. Consistent with in silico study, the analogues exhibited a greater anticancer activity against laryngeal HEP-2 cells than the original antimycin A3 with IC50 ranging of 31.6 µM to 46.3 µM. Our results clearly demonstrate that the open-chain analogues of an-timycin A3 as a promising candidates of new anti-laryngeal cancer agents.