Apoptosis-mediated antiproliferation of A549 lung cancer cells mediated by Eugenia aquea leaf compound 2',4'‑dihydroxy‑6'-methoxy‑3',5'‑dimethylchalcone and its molecular interaction with caspase receptor in molecular docking simulation

Hadisaputri,Yuni Elsa; Cahyana,Noni; Muchtaridi,Muchtaridi; Lesmana,Ronny; Rusdiana,Taofik; Chaerunisa,Anis Yohana; Sufiawati,Irna; Rostinawati,Tina; Subarnas,Anas

doi:10.3892/ol.2020.11466

Apoptosis-mediated antiproliferation of A549 lung cancer cells mediated by Eugenia aquea leaf compound 2',4'‑dihydroxy‑6'-methoxy‑3',5'‑dimethylchalcone and its molecular interaction with caspase receptor in molecular docking simulation

Authors:
- Yuni Elsa Hadisaputri
- Noni Cahyana
- Muchtaridi Muchtaridi
- Ronny Lesmana
- Taofik Rusdiana
- Anis Yohana Chaerunisa
- Irna Sufiawati
- Tina Rostinawati
- Anas Subarnas
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Affiliations: Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, West Java 45363, Indonesia, Division of Biological Activity, Laboratorium Central, Universitas Padjadjaran, West Java 45363, Indonesia, Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, West Java 45363, Indonesia, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, West Java 45363, Indonesia, Department of Oral Medicine, Faculty of Dentistry, Universitas Padjadjaran, West Java 45363, Indonesia, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, West Java 45363, Indonesia
Published online on: March 19, 2020 https://doi.org/10.3892/ol.2020.11466
Pages: 3551-3557
Copyright: © Hadisaputri et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In a previous study, 2',4'‑dihydroxy‑6'‑methoxy‑3',5'‑dimethylchalcone (ChalcEA) isolated from the leaves of Eugenia aquea was reported to inhibit proliferation of the breast adenocarcinoma MCF7 cell line and to promote apoptosis via activation of poly(adenosine diphosphate‑ribose) polymerase protein. The present study aimed to evaluate the inhibitory effect of ChalcEA on the proliferation of A549 lung cancer cells using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑5‑(3‑carboxylmethoxyphenyl)-2‑(4‑sulfophenyl)‑2H‑tetrazolium assay, and to examine the ability of ChalcEA to induce apoptosis through activation of the caspase cascade signaling pathway in a western blotting assay. The results revealed that ChalcEA inhibited proliferation of the A549 lung cancer cell lines in a time‑ and dose‑dependent manner with IC50 values of 25.36 and 19.60 µM for 24 and 48 h treatments, respectively. Western blot analysis indicated that ChalcEA exerted its anti‑proliferative effects by promoting apoptosis via the activation of caspase‑9 and caspase‑3. Based on in silico results, ChalcEA with the binding energy of ‑6.53 kcal/mol could compete better than 4‑methyl benzenesulfonamide (‑6.43 kcal/mol) as an inhibitor of caspase‑3 (PDB: 2XYG). ChalcEA has potential since it has three hydrophobic features. These results provided a basis for further study of ChalcEA as an active compound for anticancer therapeutics.

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