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Journal : The Indonesian Biomedical Journal

Andrographolide Reverses Doxorubicin Resistance in Human Breast Cancer Stem Cells by Regulating Apoptotic Gene Expressions Septelia Inawati Wanandi; Resda Akhra Syahrani; Ayu Suraduhita; Elvira Yunita; Melva Louisa
The Indonesian Biomedical Journal Vol 15, No 5 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i5.2596

Abstract

BACKGROUND: Breast cancer stem cells (BCSCs) have been identified as playing a crucial role in therapeutic resistance. This resistance can be attributed to the anti-apoptotic protein survivin and the antioxidant MnSOD high expression. To overcome the resistance to doxorubicin (DOX), this study proposed the utilization of andrographolide (ANDRO), the primary bioactive compound in Andrographis paniculata leaves. The objective was to examine the role of andrographolide in regulating survivin, caspase-9, and caspase-3 gene expressions to reverse doxorubicin resistance in human BCSCs.METHODS: BCSCs were exposed to 0.1 µM DOX every two days or 50 µM rotenone (ROT) for 6 hours, subsequently supplemented with 0.3 mM ANDRO. Superoxide and peroxide levels were measured using DHE and DCFH-DA assay. The MnSOD, survivin, caspase-9, and caspase-3 mRNA expression levels were analyzed using qRT-PCR. Protein expressions were evaluated using Western blotting assay. MnSOD activity was determined using xanthine oxidase inhibition assay. The apoptotic cells were determined using Annexin-V/PI staining.RESULTS: This study indicated that the cytotoxic mechanisms of DOX, similar to ROT, in BCSCs were attributed to oxidative stress, as evidenced by an elevation in superoxide rather than peroxide levels, accompanied by a decrease in MnSOD activity. This study also highlighted that ANDRO reversed DOX resistance in BCSCs subjected to repeated DOX treatment by downregulating survivin and upregulating caspase-9 and caspase-3 mRNA expressions, thereby activating the intrinsic apoptotic pathway.CONCLUSION: This study provides insights into the role of ANDRO in modulating the expression of apoptotic genes, such as survivin, caspase-9, and caspase-3, to overcome DOX resistance in BCSCs.KEYWORDS: breast cancer, breast cancer stem cell, andrographolide, doxorubicin, oxidative stress, apoptosis
Co-Authors -, Paramita Achmad, Fariz Adam Iskandarmudasyah Adhayati, Baety Adisti Dwijayanti Agnes Frethernety Agus D. Susanto Ahmad Aulia Ali Sodikin Amanah Amanah Anang Endaryanto Andita Fitri Mutiara Rizki, Andita Fitri Mutiara Angelica Riadi Alim Saputro Angelina Riadi Alim Saputro Anom Bowo Laksono Anton Bahtiar Anton Bahtiar Ari Estuningtyas, Ari Aria Kekalih Arini Setiawati Arini Setiawati Arleni Arleni Aurelia Demtari Tuah Ayu Suraduhita Azmi, Wihda Aisarul Barasila, Atikah Chalida Budi Setiabudiawan Budi Wiweko Clara Riski Amanda Deni Rahmat Dewi, Yulia Ratna Didi Haryadi Didi Haryadi Dina Muktiarti, Dina Elisna Syahruddin Elly Yanah Arwanih Elvira Yunita Erlina Santoso Erni H. Purwaningsih Eziefule, Oluebube Magnificient Fajri, Purnama Fasha, Iqbal Franciscus D. Suyatna Frans D. Suyatna Gayatri, Anggi Gigih Andy Putra, Achmad Ginting, Tribowo T. Halim, Kelvin Handayani, Nur Hayati Dwi HANS-JOACHIM FREISLEBEN I MADE ARTIKA Indah D Dewijanti Indah D Dewijanti, Indah D Irandi Putra Pratomo Jeanne Adiwinata Pawitan Johannes Hudyono Kania, Theresia Kato, Mitsuyasu Ketut Dewi Kumara Wati Khariri Khariri Layal, Kamalia Made Susiyanti Madoka Takeuchi Manggiasih Dwiayu Larasati Masahiro Takeuchi Mega Putri Utami Mila Maidarti Mizuno, Seiya Muhaimin Muhaimin Mulyadi Djer Nabillah, Deya Adiby Nafrialdi Nafrialdi Nasrun, Martina WS. Ni Made Dwi Sandhiutami Nihayah, Silviatun Nining Handayani Novi S. Hardiany Novita, Rachma Nur Hayati Dwi Handayani Pandelaki, Jacub Paramita - Paramita - Paramita, Paramita Perdhana, Ika S. Puspita E. Wuyung Puspita Eka Wuyung Puspita Eka Wuyung Puteri, Meidi U. Putrihamidah, Diyanthie Aulia Rachma Novita Rachma Novita Rachman, Andika Radiana Dhewayani Antarianto Raymond R. Tjandrawinata Rebecca Noerjani Angka Resda Akhra Syahrani Rianto Setiabudy Rianyta Rianyta Rika Sari Dewi Safitri, Yolanda Sake Juli Martina SEKAR ARUMSARI, SEKAR Septelia I. Wanandi Septelia Inawati Wanandi SEPTELIA INAWATI WANANDI Setiabudy, Rahajuningsih D Shafilla Yunilma Andriany Sianipar, Erlia Anggrainy Sianipar, Erlia Anggrainy Siregar, Josephine Elizabeth Siste, Kristiana Sri W.A. Jusman Sumadiono Sumadiono Suratih, Ni Made Desy Susanto, Eka Syahrani, Resda A. Syarifah Dewi Tarigan, Immanuel N. Tri Yuliani Tri Yuliani, Tri Trishna, Alya R. Ungke Antonjaya Utami, Diah S. Vivian Soetikno Vivian Soetikno Vivian Soetikno Wahyunia Likhayati Septiana Wardhani, Bantari W.K. Watanabe, Yukihide Watanabe, Yukihide Wawaimuli Arozal Widyawati, Syska Yolanda Safitri Yolanda Safitri Zakiudin Munasir