Studying the Cytotoxicity of 5-Fluorouracil Combinations, Eri Amalia Receives Doctoral Degree
Jatinangor, February 6, 2021. Eri Amalia won a Doctorate Degree in the Padjadjaran University Pharmacy Doctoral Study Program after defending her dissertation entitled “Cytotoxicity and Working Mechanism of the Combination of 5-Fluorouracil + Water Soluble Propolis and 5-Fluorouracil + Caffeic Acid Phenethyl Esters in Breast Cancer Cells. MCF-7 ”at the Open Session of Pharmacy Doctoral Study Program, Faculty of Pharmacy, Padjadjaran University, Wednesday (3/2). Eri Amalia carried out her dissertation research under Prof. Dr. Anas Subarnas M.Sc. and Prof. Dr. Ajeng Diantini M.Si. In an open session, eri must defend her dissertation in front of expert opponent Prof. Dr. Elin Yulinah Apt from ITB, Prof. Dr. Marline Abdassah from UNPAD, Dr. Med.Sc Melisa Intan Barliana from UNPAD and Prof. Dr. Ahmad Muhtadi as representatives of Unpad Professors.
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Eri revealed, currently breast cancer treatment with a combination of drugs is carried out to efficiently control and inhibit cancer growth. 5-Fluorouracil (5- FU) is a drug used in the treatment of breast cancer in combination with other anticancer drugs. However, treatment with 5-FU still has problems, especially the toxicity and side effects of the drug which are high with the dose used.
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This prompted Eri to conduct research to find new compounds to overcome these obstacles by exploring the benefits of local wisdom, namely Trigona spp. from North Luwu-South Sulawesi district, Indonesia. Propolis is made in the form of water soluble propolis (PLA), so it is expected that it contains bioactive compounds with good membrane permeability and can be developed in further pharmaceutical preparations.
Caffeic acid phenethyl ester (CAPE) is known as a bioactive compound in propolis which is found in several countries. This study was conducted to study the potential cytotoxicity of PLA and CAPE in MCF7 breast cancer cells in single and combined doses with 5-FU.
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Referring to the management of breast cancer therapy issued by the Ministry of Health of the Republic of Indonesia and the World Health Organization (WHO), 5-Fluorouracil (5-FU) is one of the drugs used in primary and second-line therapies in the treatment of breast cancer, which is used in combination. with other cancer drugs.
Therapy with a combination of drugs is an option in the treatment of breast cancer to achieve the expected pharmacological effect with side effects that are still acceptable to the patient. However, the use of 5-FU as well as the cytotoxic compounds used today still have limitations, namely the occurrence of multidrug resistance and drug toxicity which increases with the dose used. So, currently it is necessary to search for new compounds that can be developed for breast cancer therapy with low side effects.
This has led to research on a combination of anti-cancer drugs that are currently widely used clinically, namely 5-FU with natural ingredients, which have pre-clinically tested their cytotoxic activity against several types of cancer cells.
Indonesia is known as a country with the second highest biodiversity in the world after Brazil and is rich in natural resources that have the potential to be developed as medicines, including as a drug in the treatment of breast cancer. The natural material used in this study is propolis from the bee species Trigona spp. namely Tetragonula biroi originating from North Luwu Regency, South Sulawesi province. Propolis has been used homeopathically for a number of treatments including anti-tumor and anti-cancer properties.
In her research, Eri studied the potential of water soluble propolis (PLA) in inhibiting the growth of MCF-7 breast cancer cells either in single doses or in combination with 5-FU through in vitro tests with the MTT method (3- (4-5-dimethylthiazol-2yl) – 2,5- diphenyl tetrazolium bromide PLA is expected to contain polar or semi-polar compounds that have good cell membrane permeability, so that it will be easier to develop further in the manufacture of medicinal preparations, especially injection preparations commonly used in breast cancer therapy.
In this study, the cytotoxicity test of a combination of 5-FU with Caffeic acid phenethyl ester (CAPE) or 5-FU + CAPE was also carried out. CAPE is known as a bioactive compound from propolis in Brazil, India and Romania. CAPE is known to have activities such as antimicrobial, anti-inflammatory and also has cytotoxic activity on MCF-7 cells. Identification of CAPE content in crude propolis and in PLA was evaluated by the methods of High Performance Liquid Chromatography (HPLC) and Electrospray Ionization Mass Spectrometry (ESIMS). In vitro tests for the combination of 5-FU + PLA with the MTT method on MCF-7 breast cancer cells, the type of cell death due to treatment, observation of cell morphology with inverted microscopy, evaluation of caspase-8, caspase-9 and Bax mRNA expression were carried out in the same way as in the 5-FU + PLA combination test. The intrinsic apoptotic mechanism of 5-FU, PLA and CAPE was further studied by enzymatic methods, namely by looking at its potential to inhibit the activity of the enzyme human Dihidroorotate dehydrogenase (DHODH).
Through this research, Eri hopes to contribute to scientific development in the field of pharmacology, especially in finding medicinal compounds for breast cancer therapy. * (Wep)
