In vitro and in silico evaluation of Andrographis paniculata ethanolic crude extracts on 3 fatty acid synthase expression on breast cancer cells

Nur Amanina Johari, Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 8 Skudai, Johor, Malaysia.
Nur Anisa Sapi’i, Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 8 Skudai, Johor, Malaysia
Alvin Lu Jiunn Hieng, Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 8 Skudai, Johor, Malaysia
Nurriza Ab Latif, Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 8 Skudai, Johor, Malaysia
Syazwani Itri Amran, Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 8 Skudai, Johor, Malaysia
Rosnani Hasham, Institute of Bioproduct Development, Universiti Teknologi Malaysia, 81310 Skudai, Johor, 10 Malaysia
Khairunadwa Jemon, Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 8 Skudai, Johor, MalaysiaFollow

Abstract

Background Fatty acid synthase (FASN), a key rate-limiting enzyme in the fatty acid biosynthesis pathway has been identified to be overexpressed in breast cancer. This overexpression has been affiliated with poor prognosis and resistance to chemotherapeutics. Consequently, FASN has come into focus as an appealing potential target for breast cancer treatment. Available FASN inhibitors, however, are unstable and have been correlated with adverse side effects. Objective This present study aims to investigate the potential of Andrographis paniculata ethanolic crude extract (AP) as a potent FASN inhibitor in breast cancer cells. Materials & Methods This study used MTT assay and flow cytometry analysis to measure cell viability and apoptosis following AP treatment (0 – 500 μg/mL). Furthermore, FASN protein expression was evaluated using immunocytochemistry whereas lipid droplet formation was quantified using Oil Red O staining. Literature-based identified AP phytochemicals were subjected to the prediction of molecular docking and ADMET properties. Results This study demonstrated that AP significantly reduced cell viability while inducing apoptosis in breast cancer cells. In addition, for the first time, exposure to AP was demonstrated to drastically reduce intracellular FASN protein expression and lipid droplet accumulation in EMT6 and MCF-7 breast cancer cells. Docking simulation analysis demonstrated AP phytochemicals may have exerted an inhibitory effect by targeting the FASN Thioesterase (TE) domain similarly to the known FASN inhibitor, Orlistat. Moreover, all AP phytochemicals also possessed drug-likeness properties

which are in accordance with Lipinski’s rule of five. Conclusions These results highlight the potential of A. paniculata ethanolic crude extract as a FASN inhibitor and hence might have the potential to be further developed as a potent chemotherapeutic drug for breast cancer treatment.

Recommended Citation

Johari, Nur Amanina; Sapi’i, Nur Anisa; Jiunn Hieng, Alvin Lu; Latif, Nurriza Ab; Amran, Syazwani Itri; Hasham, Rosnani; and Jemon, Khairunadwa (2024) "In vitro and in silico evaluation of Andrographis paniculata ethanolic crude extracts on 3 fatty acid synthase expression on breast cancer cells," BioMedicine: Vol. 14 : Iss. 2 , Article 6.
DOI: 10.37796/2211-8039.1444