Duku (Lansium domesticum) Leaves Extract Induces Cell Cycle Arrest and Apoptosis of HepG2 Cells via PI3K/Akt Pathways

Abstract

Liver cancer is a type of malignant cancer that causes many deaths in the world. Efforts to find natural ingredients that can be used to treat liver cancer are very important. This study investigated the anticancer activity of ethanol extract of Duku (Lansium domesticum) leaves (LDE) through the cytotoxic activity, cell cycle inhibition mechanism and apoptosis influence through the PI3K/Akt pathways. Secondary metabolites of LDE were determined by common qualitative method. Cell cycle arrest was carried out by flow cytometer at inhibitory concentration 50 (IC50), while the apoptosis test was obtained using double staining method. The IC50 value was used to identifying the expression of PI3K/Akt genes. The analyzed results were proven LDE can induce HepG2 cell death which IC50 value of 19.93 ± 0.93 μg/mL (ethanol extract), 267.06 ± 3.24 μg/mL (ethyl acetate extract), and 216.47 ± 2.87 μg/mL (n-hexane extract). Cell cycle arrest activity in HepG2 cells which IC50 value of ethanol extract of LDE occurs in S phase. Observation of apoptosis occurrence was obtained getting apoptosis in cell line. PI3K/Akt genes expression of ethanol extract of LDE was obtained using RT-PCR method. The bands density of PI3K/Akt at IC50 value treatment of 0.55 ± 0.02; 0.25 ± 0.01. The LDE was determined to contain secondary metabolites which can inhibit the growth of HepG2 cells through PI3K/Akt pathways.
 HIGHLIGHTS
 
 The ethanolic extract of Lansium domesticum leaves have the best cytotoxic activity against HepG2 cells line compared to ethyl acetate extract and n-hexane extract
 The ethanolic extract of Lansium domesticum leaves have anticancer activity against HepG2 cells line through cell cycle arrest and apoptosis induce
 The ethanolic extract of Lansium domesticum leaves can inhibit the expressions of PI3K/Akt/mTOR genes using RT-PCR
 
 GRAPHICAL ABSTRACT

The ethyl acetate extract of Vernonia amygdalina leaf ameliorates gemcitabine effect against migration and invasion of PANC-1 cells via down-regulation the VEGF, COX2, and RAS/MEK pathways

“…The present study identified Annexin V positive cells as early-stage apoptotic cells, while Annexin V-PI double positive cells were identified as late-stage apoptotic cells. Necrotic cells were identified as PI single-positive cells ( Hasibuan and Sumaiyah, 2019 , Lubis et al, 2023 ).…”

Isolation of Chitosan From Dogol Shrimp Skin (Parapenaeopsis sculptilis)

“…Strong NaOH solution was one that had been used. Chitosan could still be ground to a certain size at this point, although it was still in the form of coarse granules [8]. The acetyl group (-NH-COCH3) of chitin was intended to be converted into an amine group (-NH2) in chitosan through a chitin deacetylation procedure using concentrated NaOH solvent.…”

Uji Aktivitas ALT, AST dan Histopatologi Ekstrak Etanol Rimpang Temu Kunci (Boesenbergia rotunda (L.) Mansf) pada Tikus Putih Jantan

“…Radikal bebas diproduksi dalam jumlah besar sebagai produk sampingan yang tak terhindarkan dari berbagai proses metabolisme, dan dalam kasus tertentu, seperti pada aktivasi neutrofil, akan menyebabkan meningkatnya radikal bebas dalam tubuh. Selanjutnya, radikal bebas dapat diproduksi dalam tubuh sebagai reaksi terhadap radiasi elektromagnetik dari lingkungan, dan dapat diproduksi secara langsung sebagai polutan pengoksidasi seperti ozon dan nitrogen dioksida (Lubis et al, 2023). Kerusakan dapat berkembang di berbagai jaringan jika antioksidan dalam tubuh lebih sedikit dibandingkan dengan jumlah radikal bebas.…”

“…Kelompok kontrol negatif menunjukkan rata-rata kadar AST yang paling tinggi jika dibandingkan dengan semua kelompok. Ini disebabkan karena dosis APAP 800 mg/kg BB (Lubis et al, 2023), dapat menyebabkan kerusakkan hati yang ditandai dengan peningkatan kadar AST pada serum darah hewan tikus. Akibatnya efek kerusakkan sel hati pada kelompok kontrol negatif jauh lebih besar.…”