Electronic Theses and Dissertation

Insiden kanker kolorektal menduduki peringkat ketiga sebagai kanker paling umum terjadi pada pria dan wanita di Asia Tenggara tahun 2022. Meskipun terapi kanker telah mengalami berbagai kemajuan, tantangan terkait selektivitas kemoterapi konvensional masih menjadi perhatian serius. Biji melinjo (Gnetum gnemon L.) merupakan bagian tanaman yang diketahui memiliki aktivitas antioksidan dan berpotensi dikembangkan sebagai alternatif antikanker. Pendekatan network pharmacology dapat digunakan untuk memprediksi target molekular senyawa kimia dalam biji melinjo terhadap kanker kolorektal guna menjelaskan mekanisme potensialnya dalam terapi. Penelitian ini bertujuan untuk menentukan target-target molekular tersebut, serta memvalidasi aktivitas sitotoksiknya secara in vitro. Ekstraksi dilakukan secara maserasi dengan metanol, dilanjutkan fraksinasi menggunakan n-heksana dan etil asetat. Senyawa kimia diidentifikasi menggunakan GC-MS, selanjutnya target potensial senyawa kimia dianalisis menggunakan network pharmacology serta divalidasi melalui uji MTT assay dan selectivity index (SI). Ekstrak metanol biji melinjo (EMBM), fraksi etil asetat (FEABM), fraksi n-heksana (FnHBM) dan fraksi metanol biji melinjo (FMBM) menghasilkan rendemen masing-masing 7,55%, 6,28%, 3,80% dan 56,06%. Senyawa kimia dominan yang terkandung dalam ekstrak dan fraksi biji melinjo merupakan turunan asam lemak yang menargetkan gen TP53, AKT1, dan HIF1A serta terlibat dalam jalur pathways in cancer, protein kinase activity, dan central carbon metabolism in cancer. Uji sitotoksisitas terhadap sel kanker WiDr dan perhitungan nilai SI terhadap sel Vero menunjukkan bahwa FEABM memiliki efektivitas terbaik (IC50 = 96,62 μg/mL; SI = 9,31) dibandingkan EMBM (IC50 = 864,70 μg/mL; SI = 2,24) dan FnHBM (IC50 = 167,17 μg/mL; SI = 0,89). Temuan penelitian ini menunjukkan bahwa FEABM memiliki potensi untuk dieksplorasi sebagai kandidat kemoterapi alternatif pada kanker kolorektal.

Colorectal cancer ranked third as the most commonly diagnosed cancer among men and women in Southeast Asia in 2022. Despite advancements in cancer therapy, issues related to the selectivity of conventional chemotherapy remain a major concern. Melinjo seeds (Gnetum gnemon L.) are known to possess antioxidant activity and have the potential to be developed as an alternative anticancer agent. A network pharmacology approach can be used to predict the molecular targets of chemical compounds in melinjo seeds against colorectal cancer in order to elucidate their potential therapeutic mechanisms. This study aims to determine these molecular targets and validate their cytotoxic activity through in vitro assays. Extraction was carried out using methanol maceration, followed by fractionation with n-hexane and ethyl acetate. The chemical compounds were identified using GC-MS, and potential targets were analyzed through network pharmacology and validated using MTT assay and selectivity index (SI) calculations. Methanol extract of melinjo seeds (EMBM), ethyl acetate fraction (FEABM), n-hexane fraction (FnHBM), methanol fraction (FMBM) yielded 7.55%, 6.28%, 3.80%, and 56,06% respectively. The dominant compounds identified in the extracts and fractions were fatty acid derivatives targeting TP53, AKT1, and HIF1A genes, and were involved in pathways such as cancer signaling, protein kinase activity, and central carbon metabolism in cancer. Cytotoxicity testing against WiDr colorectal cancer cells and SI calculation using Vero cells showed that FEABM had the best effectiveness (IC50 = 96.62 μg/mL; SI = 9.31) compared to EMBM (IC50 = 864.70 μg/mL; SI = 2.24) and FnHBM (IC50 = 167.17 μg/mL; SI = 0.89). These findings indicate that FEABM holds promising potential as an alternative chemotherapy candidate for colorectal cancer. Keywords: melinjo seeds, IC50, colorectal cancer, selectivity, molecular targets.