20 Original Article Cite this article: Qorina F, Arsianti A, Fithrotunnisa A, Tejaputri N, Azizah NN, Putrianingsih R. Cytotoxicity of Soursop Leaves (Annona muricata) against Cervical HeLa Cancer Cells. Pharmacog J. 2020;12(1):20-4. Phcogj.com Pharmacogn J. 2020; 12(1):20-24. A Multifaceted Journal in the feld of Natural Products and Pharmacognosy www.phcogj.com Pharmacognosy Journal, Vol 12, Issue 1, Jan-Feb, 2020 Cytotoxicity of Soursop Leaves (Annona muricata) against Cervical HeLa Cancer Cells Fona Qorina 1 , Ade Arsianti 2,3, *, Qotrunnada Fithrotunnisa 1 , NadzilaAnindya Tejaputri 1 , Norma Nur Azizah 3 , Rista Putrianingsih 2 INTRODUCTION Cancer is the leading cause of 8.8 million death globally in 2015 and ranked as the 2 nd disease with highest mortality. 1 According to National Basic Health Report (Riset Kesehatan Dasar), in 2013 the prevalence of cancer in Indonesia reached 1.4 per 1,000 population. Cancer with the highest prevalance is cervical cancer with 15,000 cases annually which make it as the leading cause of women-death in Indonesia. Cervical cancer is a type of cancer that arises from the cervical surface epithelium, located on the opening of the uterus. 2,3 Currently, modalities of treatment available for cervical cancer consist of chemotherapy, radiation, nuclear therapy, and surgery based on stadium of the cancer. Unfortunately, these treatments have several limitations due to serious side efects such as disrupting cell metabolism, nausea, vomitting, nephrotoxicity, anemia, ototoxicity. In addition, development of resistance to the drugs also considered as limitation of the current therapy. Another obstacle encountered is the expensive cost of treatments. 4 Terefore, it is necessary to develop a novel alternative therapy which is more efective and low-cost to help the patients. Indonesia is a tropical country with various natural resources, including herbal plants, that can be utilized as an alternative treatment. One of herbal plants that known has been widely used in Indonesian folk medicine is soursop (Annona muricata) (Figure 1). People commonly used its leaves to treat several conditions such as dermatitis, diarrhea, dysentry, fever, hypertension, diabetes, and also cancer. 5-7 Based on previous research conducted by Minami et al, soursop leaves extract is reported had an anticancer activity against breast cancer cells through induction of apoptotic process. 8 Another study reported that soursop leaves extracts were known to increase expression of p53 gene and lower hsp70 expression, resulted in activation of apoptosis process and stable homeostasis in Raji cells. 9 However, research about cytotoxicity of Annona muricata leaves originating from Indonesia against cervical cancer are still limited. Terefore, this research aimed to analyze cytotoxicity of A.muricata leaves against cervical cancer because it is the leading cause of cancer-related death. On the other hand, polarity of the solvents used in extraction process of herbal plant will contribute to the biological activity of the plant itself, including its cytotoxicity. Secondary metabolites contained in the plant tend to be more dissolve in the solvent with a same polarity. 10 Tus, this study also explore cytotoxicity of Annona muricata extract in three diferent polarity solvents, which are ethanol (polar), ABSTRACT Background: Cervical cancer is the cancer with highest prevalence and the leading cause of women death in Indonesia. Current treatments available for cervical cancer are chemotherapy, radiation, surgery, and nuclear therapy. Unfortunately, these treatments still have several limitations due to serious side effects, development of resistance, and very expensive price. Therefore, it is necessary to develop effective and low-cost therapy to treat cervical cancer. One of which is by utilizing natural sources available in Indonesia such as soursop (Annona muricata) leaves which has been used in folk medicine as a treatment for various diseases, including cancer. However, studies about its cytotoxicity against cervical cancer in Indonesia are still limited. Objective: The aim of this research is to analyze the potency of A.muricataleaves extracts originated from Indonesia as a novel alternative treatment for cervical cancer. Materials and method: A.muricata leaves obtained from Serpong, West Java, Indonesia were grounded and macerated in three different solvents with various polarity, namely ethanol (polar solvent), ethyl acetate (semipolar solvent) and hexane (non-polar solvent). Subsequently, the extracts were diluted into 8 various concentrations. Cytotoxicity of A.muricataleaves extracts against HeLa cervical cancer cells were determined by MTT assay and expressed by IC 50 value. Results: The results showed that three extracts of A.muricata have strong cytotoxicity against cervical HeLa cells. The highest cytotoxic activity was shown by etanol extract with an IC 50 of 35.51 µg/mL, followed by ethyl acetate (IC 50 : 5.91 µg/mL), and hexane (IC 50 : 8.39 µg/mL). Conclusion: A.muricata leaves extracts are potential to be developed as a novel alternative therapy for cervical cancer. Key words: Annona muricata, Soursop, Cytotoxicity, HeLa cells. Fona Qorina 1 , Ade Arsianti 2,3, *, Qotrunnada Fithrotunnisa 1 , NadzilaAnindya Tejaputri 1 , Norma Nur Azizah 3 , Rista Putrianingsih 2 1 Medical Student, Faculty of Medicine University of Indonesia, Depok, INDONESIA. 2 Department of Medical Chemistry, Faculty of Medicine, University of Indonesia, Depok, INDONESIA. 3 Drug Development Research Cluster, Drug Discovery Division, Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, University of Indonesia, Jalan Salemba Raya 6 Jakarta 10430, INDONESIA.. Correspondence Dr. Ade Arsianti Department of Medical Chemistry, Faculty of Medicine, University of Indonesia, Jalan Salemba Raya 6 Jakarta 10430, INDONESIA. Phone no. +6281312581253 Email: arsi_ade2002@yahoo.com History • Submission Date: 03-09-2019; • Review completed: 10-10-2019; • Accepted Date: 11-10-2019. DOI : 10.5530/pj.2020.12.4 Article Available online http://www.phcogj.com/v12/i1 Copyright © 2020 Phcogj.Com. 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