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Journal : INDONESIAN JOURNAL OF PHARMACY

In Vitro Study of the Combination of Doxorubicin, Curcuma xanthorrhiza, Brucea javanica, and Ficus septica as a Potential Novel Therapy for Metastatic Breast Cancer Sutejo, Ika Rahmawati; Putri, Herwandhani; Handayani, Sri; Jenie, Riris Istighfari; Meiyanto, Edy
Indonesian Journal of Pharmacy Vol 30 No 1, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1629.862 KB) | DOI: 10.14499/indonesianjpharm30iss1pp15

Abstract

Less optimized therapeutic effects constrain the use of doxorubicin as the main agent of chemotherapy for metastatic breast cancer, resistance and side effects. Therefore we need a combination of more than one chemopreventive agent which has different molecular targets to solve that problem. The aims of this study is to prove the inhibitory effect of ethanolic extract of rhizome of Curcuma xanthorrhiza (ECx), fruit of Brucea javanica (EBj), leave of Ficus septica (EFs) and doxorubicin (Dox) alone and its combination on migration and invasion of a highly metastatic 4T1 breast cancer cell line. Cytotoxic activity of single and combination treatment was evaluated by MTT assay, followed by an experiment of apoptosis induction by using flow cytometry. The inhibitory effect on migration was observed by the scratch wound-healing assay. Furthermore, the observation of the activity of matrix metalloproteinase-9 (MMP-9) was analyzed by gelatin zymography. The results showed that ECx, EBj, EFs, and Dox has cytotoxic activity on 4T1 cells with the value of IC50 respectively 49.7±1.53mg/mL, 59.9±1.79mg/mL, 15.2±2.12mg/mL and 1.2±0.23mM. Furthermore, combination of ECx-EBj-Dox and ECx-EBj-EFs revealed synergistic effect on 4T1 cells and decrease cell viability through the induction of apoptosis and necrosis. Based on wound healing assay, 24 hours incubation of this combination inhibited 4T1 cells migration compared to single treatment. Gelatin zymography analysis showed that this combination also inhibited the activity of MMP-9 greater than a single use. Curcuma xanthorrhiza, Brucea javanica, and Ficus septica may have potential to be developed as a combination with or without doxorubicin for metastatic breast cancer treatment.
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