Sains Malaysiana 52(9)(2023): 2657-2671

http://doi.org/10.17576/jsm-2023-5209-15

Dioscorea alata Extract as Anti-Cancer Agent by Regulating Genetic Mutations, Apoptosis, and Cell Proliferation: in vitro and in silico Studies

(Ekstrak Dioscorea alata sebagai Agen Anti-Kanser dengan Mengawal Mutasi Genetik, Apoptosis dan Pembiakan Sel: Kajian in vitro dan in silico)

SRI NABAWIYATI NURUL MAKIYAH^1,*, YUYUN IKA CHRISTINA² & AHMAD HAFIDUL AHKAM²

¹Department of Histology and Immunology, School of Medicine, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta, Yogyakarta 55183, Indonesia

²Biology Department, Faculty of Mathematics and Life Sciences, Brawijaya University, Indonesia

Received: 23 December 2022/Accepted: 5 September 2023

Abstract

Dioscorea alata (DA) tubers contain some compounds of potential anti-cancer agents. However, despite its potential, there has been limited investigation on the potential anti-cancer agent of DA, especially in breast cancer cells. Therefore, this study aims to investigate the anti-cancer effect of ethanolic extract of DA tubers against the MCF-7 cell lines in vitro and in silico. The in vitro study was carried out by cytotoxicity effect using MTT assay. The in silico study examined active ingredients, determined anti-cancer activity, analyzed the protein target, protein-protein interactions, and molecular docking. The study results showed that the high-concentration ethanolic extract of DA tubers exhibited the highest decrease in MCF-7 cell viability with an IC₅₀ value of 50.98 g/mL and can be categorized as a promising anti-cancer agent. As many as 34 active compounds belonging to anthocyanins, saponins, and flavonoids were screened. Active compounds of DA tubers with a violation score < 2 were analyzed for their biological potentials. Ten compounds of DA with the highest potency were selected for docking analysis with the targeted protein EGFR. The in-silico study showed that 21 bioactive compounds contribute to the anti-cancer activity of DA. Chlorogenic acid is the most promising bioactive compound as an anti-cancer since it is the most similar to the anti-cancer drug. Meanwhile, dihydroquercetin has a low binding affinity value, requiring less energy to bind to proteins in cancer signaling indicated that this compound is promising as anti-cancer. This study suggested that the ethanolic extract of DA tubers can be considered an anti-cancer agent against the MCF-7 cell line in vitro by regulating genetic mutations, apoptosis, and cell proliferation.

Keywords: Anti-cancer; chlorogenic acid; dihydroquercetin; Dioscorea alata; in silico

Abstrak

Ubian Dioscorea alata (DA) mengandungi beberapa sebatian agen anti-kanser yang berpotensi. Walaupun dengan potensinya, terdapat penyelidikan yang terhad mengenai potensi agen anti-kanser DA, terutamanya dalam sel kanser payudara. Oleh itu, kajian ini bertujuan untuk mengkaji kesan anti-kanser ekstrak etanol ubian DA terhadap garisan sel MCF-7 secara in vitro dan in silico. Kajian in vitro telah dijalankan melalui kesan ketoksikan menggunakan asai MTT. Kajian in silico mengkaji bahan aktif menentukan aktiviti anti-kanser, menganalisis sasaran protein, interaksi protein dan dok molekul. Keputusan kajian menunjukkan bahawa ekstrak etanol berkepekatan tinggi tuber DA mengeluarkan penurunan tertinggi dalam daya maju sel MCF-7 dengan nilai IC₅₀ sebanyak 50.98 g/mL dan boleh dikategorikan sebagai agen anti-kanser yang berpotensi. Sebanyak 34 sebatian aktif kepunyaan antosianin, saponin dan flavonoid telah disaring. Sebatian aktif ubian DA dengan skor pelanggaran < 2 telah dianalisis untuk potensi biologinya. Sepuluh sebatian DA dengan potensi tertinggi telah dipilih untuk analisis dok dengan protein yang disasarkan EGFR. Kajian in silico menunjukkan bahawa 21 sebatian bioaktif menyumbang kepada aktiviti anti-kanser DA. Asid klorogenik adalah sebatian bioaktif yang paling berpotensi sebagai anti-kanser kerana ia adalah yang paling sama dengan ubat anti-kanser. Sementara itu, dihidrokuersetin mempunyai nilai pertalian pengikatan yang rendah, memerlukan kurang tenaga untuk mengikat protein dalam isyarat kanser menunjukkan bahawa sebatian ini berpotensi sebagai anti-kanser. Penyelidikan ini mencadangkan bahawa ekstrak etanol ubian DA boleh dianggap sebagai agen anti-kanser terhadap garisan sel MCF-7 secara in vitro dengan mengawal mutasi genetik, apoptosis dan percambahan sel.

Kata kunci: Anti-kanser; asid klorogenik; dihidrokuersetin; Dioscorea alata; in silico

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*Corresponding author; email: nurul.makiyah@umy.ac.id