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Journal : UNEJ e-Proceeding

SYNERGISTIC COMBINATION OF Curcuma xanthorrhiza, Ficus septica AND DOXORUBICIN INHIBITS METASTASIS OF BREAST CANCER THROUGH INHIBITION MMP-9 ACTIVITY Ika Rahmawati Sutejo; Herwandhani Putri; Edy Meiyanto
UNEJ e-Proceeding Proceeding of 1st International Conference on Medicine and Health Sciences (ICMHS)
Publisher : UPT Penerbitan Universitas Jember

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Abstract

Breast cancer is one of the most commonmalignancy on woman in Indonesia (Kemenkes RI,2015). Breast cancer patients usually come todoctor in a late stage & the deaths are due to thecomplications of metastasis in vital organs (NationalCancer Institute, 2012). The death case mostprobably happened when cancer is aggresive &distant metastazed. One factor that causingaggresivity & metastasis is presence of HER2 protein.HER2 is found in 25% cases of Ca mammae. Her2status also influences preference of drug for cancertreatment. Besides of antibodi monoklonal &antireseptor of tirosine kinase, doxorubicin is stillused for treatment breast cancer with overexpressHER2 (Nielsen et al., 2009). Long term use ofdoxorubicin causes several side effects, resistanceand toxicity to normal tissues (Smith et al., 2010).Therefore, combining doxorubicin withchemopreventive agent is needed to increaseactivity of doxorubicin, to overcome the drugresistance and to reduce its side effect (Sarkar andLi, 2006). Chemopreventive agent used in thisresearch are temulawak (Curcuma xanthorrhiza) andawar-awar (Ficus septica). The leaves of Ficus septicahave been used to treat colds, fungal and bacterialdiseases, and various cancers. The ethanolic extractof Ficus septica showed a cytotoxic effect on breastcancer T47D cell lines with IC50 value of 13 μg/mL.The extract at 4.88 μg/mL also showed an optimumsynergistic effect in combination with doxorubicin(3.75 nmol) (Pratama et al., 2010). In addition, theextract induced apoptosis and down regulated theexpression of Bcl-2 protein in breast cancer cellsMCF-7 (Sekti et al., 2010). The major components ofC. xanthorrhiza are curcumin and xanthorrhizol.Curcumin suppresses a number of key elements incellular signal transduction pathways pertinent togrowth, differentiation, and malignanttransformation (Kunumakkara et al., 2008). Choi etal. (2005) observed that injection of 0.2-1.0 mg/kgbw xanthorrhizol had an antimetastatic effect in amouse lung metastasis model.It is a general assumption that combinationtreatment is sometimes more beneficial than singlecompounds. The previous study reported thatcombination of doxorubicin and chemopreventiveagent showed synergistic effect in cancer treatment(Lewandowska et al., 2014). The purpose of thisstudy is to prove antimetastasis effect ofcombination of ethanolic extract of rhizome ofCurcuma xanthorrhiza (ECx), ethanolic extract ofleave of Ficus septica (EFs), and doxorubicin solelyand its combination on MCF7-HER2 breast cancercell line through inhibition activity of MMP-9.Cytotoxic assay is used to determine the synergy ofcombinations. Antimetastasis effect was observedthrough inhibition of cancer cell invasion. Gelatinzymography signify the inhibitory activity of MMP-9,which plays an important role in cancer cell invasion.
Co-Authors Adistha Eka Noveyani Adji, Novan Krisno Ain Yuanita Insani Al Munawir Alief Ilman Zaelany Alief Ilman Zaelany Anaditya Wahyu Kumudhaningsih Anang Dwi Atmoko Ancah Marchianti Angga Mardro Raharjo Annafira Yuniar Annafira Yuniar Arif, Dina Rizky Amalia Arifah Nur Hasanah Avita Lukmawati Baskoro Adi Prayitno Brilliant Givya Ariansari Cholis Abrori, Cholis Diana Chusna Mufida Dimas Zabirrurohman Putra Dini Agustina Dwita Aryadina Rachmawati EDY MEIYANTO Edy Meiyanto Edy Meiyanto Edy Meiyanto ENNY SUSWATI Erfan Efendi Erma Sulistyaningsih Fauqi Amalia Fuad Adi Prasetyo Hairrudin Hairrudin Handayani, Sri Hazmi Dwinanda Nurqistan Hazmi Dwinanda Nurqistan Heni Fatmawati Heri Puguh Widodo Herwandhani Putri Herwandhani Putri Herwandhani Putri Herwandhani Putri Hilyatul Fadliyah I Nyoman Insan Parisudha Ida Srisurani Wiji Astuti Imama Rasyada Imama Rasyada Jenie, Riris Istighfari Jenie, Riris Istighfari Kiky Martha Ariesaka Kiky Martha Arieska Kristianingrum Dian Sofiana Laila Auliya Noviyanti Lailatul Maghfiroh M. Ali Shodikin Meirizky Zulharini Mudzakkir Taufiqurrqhman Ni Nyoman Yuniasih Nunung Nurhasanah Nur Hasyimiyyah Nurfahimi, Yudriani Nurul Indah Saffanah Pratikno, Dela Putri Puput Sagita Mey Sandra Putra Uta, Diego Rafi Putri, Herwandhani Rakhmat Ramadhani Rayyan, Muhammad Isra Rafidin Rini Riyanti septa surya wahyudi, septa surya Septyawati, Ratna Siti Marissa Aisyah Sugiyanta Sugiyanta Tristira Urvina Viddi Agustian Rosyidi Viddi Rosyidi Viddy Agustian Rosyidi Wiwien Sugih Utami Yasmin Auralia Putri Zahrah Febianti