The effect of ethanolic leaves extract of soursop (Annona muricata L.) on human colorectal cancer cell line: cell viability and in silico study to cyclin D1 protein

Abstract

AbstrakLatar Belakang: Kanker kolorektal merupakan transformasi patologis dari epitel kolon dan rektum normal menjadi massa jaringan abnormal, perubahan ini terjadi karena ekspresi berlebih dari protein cyclin D1 yang menginduksi proliferasi sel kolorektal secara berlebihan. Pengobatan dan pencegahan kanker kolorektal dapat dilakukan secara alami dengan mengonsumsi ekstrak daun Annona muricata L. (sirsak). Sirsak dikenal karena banyak komponen fitokimia yang berfungsi sebagai anti kanker. Metode: Penelitian ini menggunakan sel kanker kolorektal HT-29 yang diberi ekstrak etanol daun sirsak dan . Tujuannya untuk menemukan konsentrasi sitotoksisitas yang dapat menghambat 50% populasi sel dan konsentrasi yang didapat sebelumnya akan diuji dengan metode uji MTT. Analisis docking molekuler dilakukan antara molekul-molekul dari ekstrak etanol daun sirsak terhadap protein Cyclin D1 menggunakan perangkat lunak molecular operating environment (MOE) 2013.08. Hasil: CC50 ekstrak etanol daun sirsak adalah 278 μg / mL dan 5-FU adalah 88 μg / mL. Persentase terendah sel HT-29 yang layak adalah 2 x CC50 setelah perlakuan ekstrak etanol daun sirsak (40,4 ± 1,3%) dibandingkan dengan 5-FU (52,8 ± 4,3%), kontrol pelarut ( 97,2 ± 1,4%), dan kontrol sel (100%). Analisis docking molekuler untuk protein cyclin D1 diperoleh asam N-hexadecanoic dan molekul phytol sebagai kandidat yang baik untuk menghambat protein cyclin D1. Kesimpulan: Ekstrak etanol daun sirsak dapat menurunkan viabilitas sel kultur kanker kolon HT-29 dan berdasarkan analisis molekular docking dilihat dari energi bebas gibbs (ΔG) dan afinitas tertinggi (pKi) diperoleh N-hexadecanoic dan molekul phytol sebagai penghambat protein cyclin D1. (Health Science Journal of Indonesia 2019;10(2):96-102) Kata Kunci: Kanker kolorektal HT-29, ekstrak etanol daun sirsak, viabilitas sel, molecular docking, cyclin D1Abstract Introduction: Colorectal cancer is a pathological transformation of normal colon and rectum epithelial that becomes an abnormal tissue mass, due to the overexpression of cyclin D1 protein that inducing excessive proliferation of colorectal cell. The treatment and prevention of colorectal cancer could be done naturally by consuming leaves extract of Annona muricata L. (soursop). Soursop is known for many phytochemical components that serve as an anti-cancer. Methods: This study was used HT-29 colorectal cancer cell that treated with ethanolic leaves extract of soursop and 5-Fluorourasil (5-FU) to find the cytotoxicity concentration that can inhibit 50% of HT-29 cell population (CC 50 ) and the next concentrations of them were treated for next treatment with MTT assay. Molecular docking analysis of the compounds of ethanolic leaves extract of soursop to cyclin D1 protein used molecular operating environment (MOE) 2013.08 software. Results: CC 50 of ethanolic leaves extracts of soursop was 278 µg/mL dan 5-FU was 88 µg/mL. The lowest percentage of viable HT-29 cell was 2 x CC 50 after ethanolic leaves extract of soursop treatment (40,4±1,3%) was compared to 5-FU (52,8...

Potential of Indonesian Herbal as an Anti-Cancer Therapy: A Systemic Review of in vitro Studies

“… 17 +2 +2 +2 +2 +2 +2 +2 +1 +1,875 1 Low Risk of Bias Abdullah M, dkk. 18 +2 +2 +2 +2 +2 +2 +2 +1 +1,875 1 Low Risk of Bias Bhanuwati AV and Pakpahan A. 19 +2 +2 +2 +2 +2 +2 +2 +1 +1,875 1 Low Risk of Bias Ramandhita AP, dkk.…”

“… Abdullah M, dkk. 18 2019 S2 Annona muricata (Soursop) Note: Ethanol extract West Java HT-29 cell Colorectal cancer MTT Assay Inhibits the activity of cyclin protein D1 CC50 soursop leaf ethanol extract is 278 μg/mL Soursop leaf ethanol extract may decrease the viability of HT-29 colon cancer cells 7. Bhanuwati AV and Pakpahan A.…”

“…When compared to its presence in soursop leaves, the phytochemical content of soursop fruit, which includes alkaloids, annonaceous acetogenin compounds (AGEs), and phenols, demonstrates that each phytochemical category has a smaller variance in the fruit. 17 Soursop has the potential to be anti-cancer 14,15,[17][18][19]31 because it contains various compounds such as flavonoids, AGEs, and alkaloids that have anticancer capabilities. AGEs have the ability to inhibit mitochondrial complex I which can inhibit the formation of adenosine triphosphate (ATP), resulting in a decrease in ATP in cancer cells so that it can inhibit proliferation and induce apoptosis of cancer cells.…”

The Effects of Simvastatin and Soursop (Annona muricata) Leaf Extract on Colorectal Cancer

“…Studies have shown that extract of A. muricata leaves exerts cytotoxic effects, mostly in a dose-and time-dependent manner, against various CRC cell lines, and in tumor xenograft models. Studies have demonstrated that extract of A. muricata leaves was capable of suppressing CRC cell growth and proliferation (Moghadamtousi et al, 2014;Moghadamtousi et al, 2015), inducing apoptosis (Abdullah et al, 2019;Awad et al, 2020;Moghadamtousi et al, 2014;Moghadamtousi et al, 2015), promoting cell cycle arrest at G1 phase (Moghadamtousi et al, 2014), promoting cell cycle arrest at G2/M phase (Awad et al, 2020), repressing cell migration and invasion (Moghadamtousi et al, 2014), and reducing tumor size and volume (Moghadamtousi et al, 2015).…”

“…Possible mechanisms of A. muricata leaf extract includes activation of apoptosis intrinsic pathway via upregulation of pro-apoptotic BAX expression and downregulation of antiapoptotic BCL2 expression (Abdullah et al, 2019;Awad et al, 2020;Moghadamtousi et al, 2014;Moghadamtousi et al, 2015). Other possible mechanisms were cytochrome cmediated apoptosis through cytochrome c release, initiation of programmed cell death and mitochondria-mediated apoptosis through induction of lactate dehydrogenase (LDH) leakage, depletion of mitochondrial membrane potential (MMP), and induction of DNA fragmentation (Moghadamtousi et al, 2014;Moghadamtousi et al, 2015).…”