One of the compounds found effication as an anticancer agent on cervical cancer is acetogenin, a polyketide compound that is abundant in Annona muricata L. leaves. This study has been done to examine polyketide derivatives was isolated from Annona muricata L. which has potency to induce apoptosis by p53 expression on hela cell line. An approach recently develop to overcome side effect of chemoterapeutic agent is used of combined chemoterapeutic agent, i.e doxorubicin. The determination of cytotoxic combination activity from polyketide derivative and doxorubicin was evaluated using MTT assay to obtain the value of CI (combination index). The expression of p53 profile was evaluated by immunohistochemistry on hela cell line. Data analysis showed that combination of polyketide derivative from Annona muricata L. (38,5 µg/ml) and doxorubicin with all of concentration performed synergistic effect on hela cell line with CI value from 0,33 – 0,65. The analysis on immucytochemistry showed that polyketide derivative from Annona muricata L. leaves could enhance p53 pathway significantly on hela cell line.

https://iopscience.iop.org/article/10.1088/1757-899X/176/1/012002/pdf

Polyketide Derivatives from Annona muricata Linn Leaves as Potencial Anticancer Material by Combination Treatment With Doxorubicin on Hela Cell Line

https://mail.phcogj.com/sites/default/files/PJ-12-1-224_0.pdf

Cytotoxicity of soursop leaves (Annona muricata) against cervical HeLa cancer cells

Soursop leaf chloroform extract has anticancer activity.  The active ingredient of soursop leaf was acetogenin polypoid derivatives that have a lipophilic characteristic, and less effective to achieve action targets of drugs in biological systems. The Self-Micro Emulsifying Drug Delivery System (SMEDDS) was an effective drug delivery technique that increases the solubility of lipophilic drugs. This study aims to determine the proportion of optimum SMEDDS formula using Simplex Lattice Design (SLD) method. The Formula of SMEDDS was prepared using a combination of Tween 80-Croduret, Propylene Glycol, and Candlenut oil. Optimization formula with SLD method using Design-Expert software based on physical stability parameters there are the percent of transmittance and emulsification time. The optimum formula of SMEDDS was compared with SLD prediction formula using a statistical analysis t-test, then test of loading dose extract, stability test accelerated by centrifugation, particle size, and zeta potential. The proportion of optimum composition of Tween 80-Croduret, Propylene Glycol, and Candlenut oil of SMEDDS was 60.87%; 24.13%; 15.00% respectively. Results of transmittance 41.14±3.78% and emulsification time 119.0±2.08 seconds. The predicted SLD value for the transmittance percent was 55.0% and the emulsification time was 119.59 seconds. The result of the statistical analysis of one sample t-test showed no significant difference between observation results and SLD prediction. The SMEDDS system has F value of 0.99 and capable to load 25.0 mg chloroform extract of soursop leaf each system with an average particle size of 440 nm and zeta potential of +21.5 mV.

https://jurnal.ugm.ac.id/TradMedJ/article/download/51590/28958

Optimization of Self-Micro Emulsifying Drug Delivery System) for Soursop Leaf (Annona muricata Linn.) Chloroform Extract

Abstract: Polycyclic aromatic hydrocarbons (PAH) is one of the largest group of carcinogen in the environment.  An agent that has antigenotoxic and anticarcinogen potency is needed to prevent DNA damage and carcinogenesis. Soursop leaves have a chemopreventive action. This study was aimed to assess the effectiveness of ethanolic extract of soursop leaves in prevention of dysplasia of upper surface of tongue in rats. This was a true laboratory experimental study with the post test-only control group design, using 24 male Sprague Dawley rats divided into six groups. The upper surfaces of tongues of group I-III were induced by DMBA topically three times a week for 16 weeks; group II and III were induced by DMBA added soursop leaves ethanolic extract of 100 and 200 mg/kg body weight daily for 18 weeks; group IV was given soursop leaves ethanolic extract 200 mg/kg body weight; group V was given DMSO 1%; and group VI was untreated. After 18th week, rats were terminated and tongue necropsies in longitudinal anteroposterior direction were conducted. The clinical changes of the upper surfaces of the tongues were observed and the histological changes were observed by using HE staining to confirm signs of dysplasia. The Kruskal Wallis test showed differences between groups, and the Mann-Withney test showed not significantly decrease of mild dysplasia of group II and group III compared to group I (p>0.05). In conclusion, ethanolic extract of soursop leaves was not effective in prevention of dysplasia of the upper surface of rat’s tongue.Keywords: dysplasia; soursop leave extract; dorsal part of tongue; DMBA  Abstrak: Senyawa golongan PAH merupakan salah satu kelompok karsinogen terbesar di lingkungan. Sebagai upaya untuk mencegah kerusakan DNA serta karsinogenesis, diperlukan suatu agen yang berpotensi antigenotoksik sekaligus antikarsinogenik. Daun sirsak terbukti mempunyai aksi kemopreventif. Penelitian ini bertujuan untuk mengkaji efektivitas ekstrak etanol daun sirsak dalam mencegah displasia pada dorsum lingue tikus. Jenis penelitian ialah true experimental laboratory dengan the post test-only control group design yang menggunakan 24 ekor tikus galur Sprague Dawley jantan, dibagi dalam enam kelompok. Dorsum lingue tikus kelompok I - III diinduksi DMBA secara topikal tiga kali seminggu selama 16 minggu; kelompok II dan III selain diinduksi DMBA, juga diberi ekstrak etanol daun sirsak 100 dan 200 mg/kg berat badan setiap hari selama 18 minggu; kelompok IV diberi ekstrak etanol 200 mg/kg BB; kelompok V diberi DMSO 1%; dan kelompok VI tidak diberi perlakuan. Terminasi dan nekropsi lidah tikus longitudinal anteroposterior dilaksanakan setelah minggu ke 18. Perubahan pada dorsum lingue diamati secara klinis dan perubahan histologik dilihat dengan pewarnaan HE untuk mengonfirmasi tanda displasia. Uji Kruskal Wallis menunjukkan perbedaan antar kelompok, sedangkan uji Mann Whitney menunjukkan penurunan tidak bermakna displasia ringan pada kelompok II dan III dibanding kelompok I. Simpulan penelitian ini ialah ekstrak etanol daun sirsak tidak efektif dalam mencegah displasia epitel dorsum lingue tikus.Kata kunci: displasia; ekstrak daun sirsak; dorsum lingue; DMBA

/pdf/efektivitas-ekstrak-etanol-daun-sirsak-annona-muricata-linn-4g22zsckij.pdf

Efektivitas Ekstrak Etanol Daun Sirsak (Annona muricata Linn) dalam Mencegah Displasia Dorsum Lingue Tikus Galur Sprague Dawley yang Diinduksi 7,12 Dimetilbenz(Α)Antrasena

Purpose: Organic extracts of plant Annonaceae enhances apoptosis in animal cells and get the drives to reach a new homeostasis. The incidence rate of nasopharyngeal cancer in Indonesia is quite high. Protein 53Kd (p53) play a role in apoptosis process, being heat shock protein 70 (hsp70) play a role in homeostasis. The aim of this research is to identify the apoptotic effects of Annona muricata Linn leaf toward Raji cells by observing the p53 and hsp70 expression. Methods : Apoptotic assay was performed in 24 wells micro-culture plate. Raji cells were prepared as 2 × 10 4 cells in 100 ml RPMI media per well. Roswell Park Memorial Institute (RPMI) medium was created and solvent was controlled with Dimethyl Sulfoxide (DMSO) solvent 0.25. Apoptotic test was performed by calculating trypan-blue-dye exclution. The cells were then grown in micro-culture plate with media plus extract non-lethal concentration of partition and fractionation of Annona muricata Linn leaf. The sampling was performed for 24 hours. The number of living cells was calculated in each of these well and incubation time were determined. Immunohistochemical staining was done to identify the expression of p53 and hsp70. Results: The results showed that Raji cells treated with partition of Annona muricata Linn leaf in ethyl acetate solvent 133.00 % resulted in higher apoptosis. Another results showed that Raji cells treated with fractionation Annona muricata Linn leaf in ethyl acetate solvent 103.20 % resulted in higher apoptosis. The expression of p53 after treatment with fractionation Annona muricata Linn leaf was higher than before while hsp70 expression after treatment with fractionation Annona muricata Linn leaf was lower. Conclusion : The conclusion is the higher the dose of Annona muricata Linn the higher the p53 expression thereby activates apoptosis process The higher dose of Anonna muricata Linn also leads to lower hsp70 expression indicating stable homeostasis of Raji cells. ---------------------------------------------- Cite this article as: Astirin OP, Prayitno A, Artanti AN, Fitria MS, Witianingsih DA, Pranatami DA, Putra ST. The expression of p53 and hsp70 proteins after treatment with Annona muricata Linn leaf for activating apoptotic and lead to homeostasis program of Raji cells. Int J Cancer Ther Oncol 2014; 2(2):02028. DOI: 10.14319/ijcto.0202.8

The expression of p53 and hsp70 proteins after treatment with Annona muricata Linn leaf for activating apoptotic and lead to homeostasis program of Raji cells

Dyah Ayu Witianingsih

Papers

The expression of p53 and hsp70 proteins after treatment with Annona muricata Linn leaf for activating apoptotic and lead to homeostasis program of Raji cells