DHONA, AFRIZA (2018) POTENSI ANTIKANKER NORDENTATIN TERHADAP APOPTOSIS CELL LINES HSC-4 KARSINOMA SEL SKUAMOSA RONGGA MULUT SECARA IN SILICO DAN IN VITRO. Doctoral thesis, Universitas Andalas.
|
Text (COVER & ABSTRAK)
COVER & ABSTRAK.pdf - Published Version Download (500kB) | Preview |
|
|
Text (PENDAHULUAN)
13 Bab 1.pdf - Published Version Download (494kB) | Preview |
|
|
Text (PENUTUP)
20 BAB 7.pdf - Published Version Download (323kB) | Preview |
|
|
Text (DAFTAR PUSTAKA)
21 DAFTAR PUSTAKA.pdf - Published Version Download (635kB) | Preview |
|
![[img]](http://scholar.unand.ac.id/style/images/fileicons/text.png) |
Text (DISERTASI)
ki utuh.pdf - Published Version Restricted to Repository staff only Download (12MB) |
Abstract
Oral Squamous Cell Carcinomas are the most common cancers in the world and has a high rate of recurrence and mortality. The therapy has been given often causes side effects such as discomfort and chemoresistant against cancer cells. Some natural compounds have been reported have a potential chemosensitivity effect, relatively non-toxic and inexpensive. Nordentatin is a natural compound derived from the Clausena excavata plant. Several literatures reported that nordentatin compounds exhibit high cytotoxicity against cancer cells. The effects of nordentatin on genes that trigger apoptosis of OSCC cells have not been reported. The molecular mechanisms underlying the anticancer of nordentatin remain unclear. Therefore, the aim of this study was to investigate the anticancer potential of nordentatin in vitro and in silico in triggering apoptosis either through intrinsic or extrinsic pathways on cell line HSC-4 OSCC. The study was conducted in four stages, beginning with the cytotoxicity of nordentatin on HSC-4 cell lines, followed by flowcytometry to determine the effect of nordentatin on apoptosis of HSC-4 cell lines. This study was followed by the in silico analysis of nordentatin ligand against apoptosis proteins (Bcl-2, EGFR, NFkB, Survivin, Caspase-3 and Caspase-7) with molecular docking to determine reactions of nordentatin with some proteins involved in apoptosis. Furthermore, a study was conducted to determine the activities of Caspase-3 and Caspase-7 after being treated with Nordentatin to confirm the results of molecular docking that has been done. The results showed the cytotoxicity of nordentatin against HSC-4 cell lines with IC50 values of 68 μg / mL. Apoptosis that occurred on induction with nordentatin were 47.30%, doxorubicin were 13.71% and control were 3.73%. The statistical test showed significant results with ρ = 0.008. In silico analysis has been performed to determine the reactions between nordentatin, doxorubicin and quercetin with anti-apoptotic proteins (Bcl-2, EGFR, NFkB, Survivin) and pro-apoptosis (Caspase-3 and Caspase-7) suggesting that nordentatin can react with all protein and produce a good affinity binding. Binding affinity between nordentatin and apoptotic proteins Bcl-2, EGFR, NFkB, Survivin, Caspase -3 and Caspase -7 were -7.3, -8.2, -6.3, -6.5, -6.6, and -6.2 kcal / mol respectively. The results of Caspase-3 and Caspase-7 activity analysis showed that Nordentatin induces Caspase -3/-7 activity better than doxorubicin and control. The statistical test shows a significant difference with ρ = 0,000. Based on the results of research that has been done both in silico and in vitro can be concluded that nordentatin has the potential as an anticancer because it can trigger apoptosis through intrinsic or extrinsic pathway of HSC-4 cell lines Oral Squamous Cell Carcinoma. Keywords: nordentatin, cytotoxicity, apoptosis, molecular docking, oral cancer
| Item Type: | Thesis (Doctoral) |
|---|---|
| Primary Supervisor: | Prof. Dr. dr. Yanwirasti, PA (K) |
| Subjects: | R Medicine > RS Pharmacy and materia medica |
| Divisions: | Pascasarjana (Disertasi) |
| Depositing User: | s3 Biomedik kedokteran |
| Date Deposited: | 21 May 2019 12:49 |
| Last Modified: | 21 May 2019 12:49 |
| URI: | http://scholar.unand.ac.id/id/eprint/44783 |
Actions (login required)
 |
View Item |
