STUDY OF CYTOTOXIC ACTIVITY OF SEVERAL PLANTS Uncaria spp. FROM RIAU ON BREAST CANCER CELLS: ISOLATION, MOLECULAR DOCKING AND IN VITRO STUDY OF TERPENOIDS FROM Uncaria nervosa Elmer.

Rahmawati, Noveri (2024) STUDY OF CYTOTOXIC ACTIVITY OF SEVERAL PLANTS Uncaria spp. FROM RIAU ON BREAST CANCER CELLS: ISOLATION, MOLECULAR DOCKING AND IN VITRO STUDY OF TERPENOIDS FROM Uncaria nervosa Elmer. S3 thesis, Universitas Andalas.

	Text (Cover dan Abstrak) Abstrak.pdf - Published Version Download (328kB)
	Text (Bab 1) BAB I. Pendahuluan.pdf - Published Version Download (179kB)
	Text (Bab Penutup) Bab VII. Penutup.pdf - Published Version Download (116kB)
	Text (Daftar Pustaka) Daftar Pustaka.pdf - Published Version Download (218kB)
	Text (Disertasi Fulltext) Disertasi Full Text.pdf - Published Version Restricted to Repository staff only Download (12MB)

Abstract

Breast cancer is one of the most common diseases found in women today. Breast cancer occurs due to damage to growth and differentiation genes so that these cells can grow and develop uncontrollably. Cancer management such as giving anticancer drugs, chemotherapy, x-rays and surgery, requires expensive costs, and the patient's recovery rate after going through these stages is also relatively low. This treatment is still not specific because it can cause other normal cells to be killed, so it is necessary to develop new drugs that have selective therapeutic effects as anticancer drugs by exploring natural compounds derived from plants, including Uncaria nervosa Elmer. The Uncaria nervosa Elmer plant is a plant that is the local wisdom of Riau Province and traditionally, this plant is used to treat cancer. This study was conducted with stages, namely screening of cytotoxic activity of 4 Uncaria spp species on T47D breast cancer cells, isolation using the bioassay guided isolation method using the metabolite profile approach, molecular docking studies of pure compounds, determination of cytotoxic activity, apoptosis and protein expression of pure compounds. Determination of cytotoxic activity was carried out using the MTT method, determination of metabolite profiles using LCMS/MS, purification of compounds was carried out using preparative recycling HPLC, induction of apoptosis was carried out using the double staining method and determination of Bcl-2 protein expression was carried out using the Western blot method. In the research that has been conducted, the results obtained that the ethanol extract of Uncaria nervosa Elmer leaves has the most potent cytotoxic activity on T47D breast cancer cells. This extract is predicted to contain 9 compounds which are alkaloids, fatty acids, triterpenoids and diterpenoids. The ethanol extract was fractionated and the ethyl acetate fraction was selected to continue the isolation process. The isolation results obtained six isolates which are alkaloids, triterpenoids and steroids, and the isolates that were elucidated were isolates number three and four which are betulinic acid and ursolic acid compounds. These two compounds were determined for cytotoxic activity, apoptosis induction and Bcl-2 protein expression in MCF-7/HER2 breast cancer cells. Based on the research that has been conducted, it can be concluded that the ethanol extract of Uncaria nervosa Elmer leaves has the most potent cytotoxic activity on T47D breast cancer cells. The predicted metabolite profile in the ethanol extract of Uncaria nervosa Elmer leaves is nicometh, 3-methoxy-2-methylpyridine, 1,1-dichloro-1-nitrosopropane, glucosol, betulonic acid, ursolic acid, 7-methyl-N-[6-[(7-methyl-6-oxooctanoyl) amino] hexyl]-6-oxononanamide, nervisterol and 3,5,10-tris(acetyloxy)-2-hydroxy-4,14,16,16-tetramethyl-8-methylidene-13-oxo-15oxatetracyclo[9.4.1.0¹,¹⁴.0⁴,⁹]hexadecan-7-yl 3-phenylprop-2-enoate. There were 6 compounds that were successfully isolated but the ones that were elucidated were two compounds that were triterpenoids, namely betulinic acid and ursolic acid. The results of molecular docking of betulinic acid and ursolic acid compounds on the Bcl-2 protein inhibitor (2W3L) show that both compounds can inhibit Bcl-2 protein expressionThese two compounds have the potential to be cytotoxic to MCF-7/HER2 breast cancer cells with a moderate activity category, where the IC50 value is < 20 μg/mL and can induce apoptosis in MCF-7/HER2 breast cancer cells. Keywords: Apoptosis, Bcl-2 protein expression, molecular docking, recycling preparative HPLC, T47D cells, MCF-7/HER2 cells, sirius platform, Uncaria nervosa Elmer

Item Type:	Thesis (S3)
Supervisors:	1. Prof. apt. Dachriyanus, Ph.D 2. Prof. Dr. Nor Hadiani Ismail 3. Prof. apt. Fatma Sri Wahyuni, Ph.D
Uncontrolled Keywords:	Apoptosis, ekspresi protein Bcl-2, molecular docking, recycling preparative HPLC, sel T47D, sel MCF-7/HER2, sirius platform, Uncaria nervosa Elmer
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisions:	Fakultas Farmasi > S3 Farmasi
Depositing User:	s3 farmasi farmasi
Date Deposited:	31 Dec 2024 06:56
Last Modified:	31 Dec 2024 06:56
URI:	http://scholar.unand.ac.id/id/eprint/484774

Actions (login required)

View Item