Development of Co-Chemotherapeutic Agents and Analysis of the Active Substance Content of Red Ginger (Zingiber officinale Var Rubrum rhizoma) in Metastatic Breast Cancer Cells

Laili Nailul Muna, Enny Riyan Hasni, Farhatul Uyun, Erna Wulandari

Abstract


Metastatic breast cancer also known as stage IV breast cancer. Current chemotherapy agents have several limitations, such as resistance events, side effects, and inadequate efficacy in advanced cancer. It is necessary to develop a more effective chemotherapy model, namely the development of co-chemotherapy agents derived from natural ingredients that have activity in counteracting oxidative stress and preventing metastatic breast cancer, namely red ginger. GC-MS analysis of red ginger oleoresin showed the composition of chemical compounds influenced by variants of soxletation time of 60, 120, and 180 minutes. GC-MS analysis showed that this essential oil consists of volatile compounds, mainly from the sesquiterpene group and namely zingiberene, betha-sesquiphellandrene, betha-bisabolene and ar-curcumene. The results of the cytotoxic test analysis of red ginger extract with socletation time for 60, 120 and 180 minutes respectively obtained IC50 data as follows with 45.16 µg/ml, 37.23 µg/ml and 20.2 µg/ml. The compounds contained in red ginger, such as zingiberene, gingerol, shogaol, flavonoids, phenolics, alkaloids, saponins, and tannins, play an important role in its cytotoxic effect against cancer cells. The mechanism by which alpha-Zingiberene induces cell death in cancer cells is mainly through the apoptotic process. The compound causes the release of mitochondrial cytochrome c into the cytoplasm, which then activates caspase-3, an apoptotic enzyme.

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Ahlina, F. N., Nugraheni, N., Salsabila, I. A., Haryanti, S., Da’i, M., & Meiyanto, E. (2020). Revealing the reversal effect of galangal (Alpinia galanga L.) extract against oxidative stress in metastatic breast cancer cells and normal fibroblast cells intended as a Co- chemotherapeutic and anti-ageing agent. Asian Pacific Journal of Cancer Prevention, 21(1), 107–117. https://doi.org/10.31557/APJCP.2020.21.1.107

Amin, S., Lestari, S. L., & Agustin, S. C. (2025). Analisis Kandungan Minyak Atsiri Jahe ( Zingiberis Officinalis Rhizoma ) Menggunakan Kromatografi Spektrometer Massa. 5(3), 47–53.

Angraini, S. M., Nugraheni, N., Meiyanto, E., & Hermawan, A. (2019). Analog Curcumin, Pentagamavunon-0 (PGV-0), Induces Senescence and Increases Cytotoxic Effect of Doxorubicin on HCC 1954 Cells. Indonesian Journal of Cancer Chemoprevention, 10(3), 114. https://doi.org/10.14499/indonesianjcanchemoprev10iss3pp114-121

Ashariati, A. (2019). Manajemen Kanker Payudara Komprehensif. Journal of Chemical Information and Modeling, 53(9), 1689–1699.

Azian, M. N., Anisa, A. N. I., & Iwai, Y. (2014). Mechanisms of Ginger Bioactive Compounds Extract Using Soxhlet and Accelerated Water Extraction. International Journal of Chemical, Molecular, Nuclear, Materials and Metallurgical Engineering, 8(5), 444–448.

Bryant, Puspitaningtyas, H., Wiranata, J. A., Hutajulu, S. H., Widodo, I., Anggorowati, N., Sanjaya, G. Y., Lazuardi, L., & Sripan, P. (2023). Breast cancer incidence in Yogyakarta, Indonesia from 2008–2019: A cross-sectional study using trend analysis and geographical information system. PLoS ONE, 18(7 JULY), 1–17. https://doi.org/10.1371/journal.pone.0288073

Dwi Oktaviani, N. (2020). Journal of Pharmaceutical and Sciences Cytotoxic Potential of Red Ginger Rhizome Extract (Zingiber officinale var. rubrum) Against 4T1 Breast Cancer Cells Potensi Sitotoksik Ekstrak Rizoma Jahe Merah (Zingiber officinale var. rubrum) terhadap Sel Kanker P. Jps, 2025(2), 706–715. https://doi.org/10.36490/journal-jps.com.v8i2.796

Fachreza Erdi Pratama, & Rina Fajri Nuwarda. (2018). Review: Senyawa Aktif Antikanker Dari Bahan Alam Dan Aktivitasnya. Farmaka, 16(01), 149–158.

Feng, Y., Spezia, M., Huang, S., Yuan, C., Zeng, Z., Zhang, L., Ji, X., Liu, W., Huang, B., Luo, W., Liu, B., Lei, Y., Du, S., Vuppalapati, A., Luu, H. H., Haydon, R. C., He, T. C., & Ren, G. (2018). Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes and Diseases, 5(2), 77–106. https://doi.org/10.1016/j.gendis.2018.05.001

Ghasemi, M., Turnbull, T., Sebastian, S., & Kempson, I. (2021). The mtt assay: Utility, limitations, pitfalls, and interpretation in bulk and single-cell analysis. International Journal of Molecular Sciences, 22(23). https://doi.org/10.3390/ijms222312827

Ghasemzadeh, A., Jaafar, H. Z. E., & Rahmat, A. (2015). Optimization protocol for the extraction of 6-gingerol and 6-shogaol from Zingiber officinale var. rubrum Theilade and improving antioxidant and anticancer activity using response surface methodology. BMC Complementary and Alternative Medicine, 15(1). https://doi.org/10.1186/s12906-015-0718-0

Hairunisa, I., Bakar, M. F. A., Da’i, M., Bakar, F. I. A., & Syamsul, E. S. (2023). Cytotoxic Activity, Anti-Migration and In Silico Study of Black Ginger (Kaempferia parviflora) Extract against Breast Cancer Cell. Cancers, 15(10), 1–16. https://doi.org/10.3390/cancers15102785

Handayani, S. S., Gunawan, E. R., Suhendra, D., & Murniati, M. (2024). Kajian Pengaruh Suhu Pemanasan Awal Dan Waktu Sokletasi Terhadap Perolehan Minyak Biji Kelor (Moringa Oleifera Lam.). Jurnal Sains Teknologi & Lingkungan, 10(4), 749–754. https://doi.org/10.29303/jstl.v10i4.754

Hikmah, F., Hardiany, N. S., & Kunci, K. (2021). Peran Reactive Oxygen Species (ROS) Dalam Sel Punca Kanker The Role of Reactive Oxygen Species (ROS) in Cancer Stem Cells. Jurnal Kedokteran Yarsi, 29(3), 120–134.

Ida, N., Rusli, & Sriyanti. (2024). Formulasi Edible Film Antibakteri Ekstrak Daun Cengkeh (Syzygium aromaticum L.) Dengan Variasi Konsentrasi Sorbitol Sebagai Plasticizer. Media Farmasi, 20(1), 1–10. https://doi.org/10.32382/mf.v20i1.185

Kriswiyanti, E., Darsini, N. N., Hardini, J., & Ariwathi, N. P. (2021). Keanekaragaman Jenis Tumbuhan Bahan Ramuan “Boreh Basanbuat” Untuk Memperlancar Produksi Air Susu Ibu (ASI) di Bali. Metamorfosa: Journal of Biological Sciences, 8(2), 304. https://doi.org/10.24843/metamorfosa.2021.v08.i02.p15

Lee, Y. (2016). Cytotoxicity evaluation of essential oil and its component from Zingiber officinale Roscoe. Toxicological Research, 32(3), 225–230. https://doi.org/10.5487/TR.2016.32.3.225

Machana, S., Weerapreeyakul, N., Barusrux, S., Nonpunya, A., Sripanidkulchai, B., & Thitimetharoch, T. (2011). Cytotoxic and apoptotic effects of six herbal plants against the human hepatocarcinoma (HepG2) cell line. Chinese Medicine, 6, 2–9. https://doi.org/10.1186/1749-8546-6-39

Maspupah, T., Nina, N., Siagian, T. D., Pakhpahan, J., & Octavianie, G. (2022). Perilaku Pencegahan dan Risiko Kejadian Diabetes Melitus Tipe 2 pada Usia Produktif di Kabupaten Bogor Tahun 2021. Journal of Public Health Education, 2(1), 242–253. https://doi.org/10.53801/jphe.v2i1.66

Maulida, M. Z., Ummahati, D., & Muna, L. N. (2023). Analisis Sifat Fisikokimia, Farmakokinetik, Dan Toksisitas Senyawa Aktif Dalam Jahe Merah (Zingiber Officinale Var Rubrum Rhizoma). Journal Pharmaceutical Care and Sciences, 4(1), 90–98. https://doi.org/10.33859/jpcs.v4i1.454

Mawadah, I. (2024). Molecular Docking of Zingiber officinale var . Rubrum Compounds with DDX3X ( Dead-Box Helicase 3x-Linked ) as Anticancer Compound. 1(1), 17–22.

Muna, L. N., & Maulidina, F. (2022). Penghambatan Proliferasi Sel Kanker Payudara T47D oleh Ekstrak Air Daun Kelor (Moringa oleifera) dan Doxorubicin dengan Metode MTT Assay. Jurnal Farmasi Sains Dan Terapan, 9(2), 99–104. https://doi.org/10.33508/jfst.v9i2.4361

Mutia, L., Meutia, N., Ichwan, M., Sari, M. I., & Siregar, Y. (2019). Polimorfisme Gen Reseptor Vitamin D Cdx 2 (rs 11568820) pada Penderita Kanker Payudara di Rumah Sakit Umum Pusat Haji Adam Malik Medan. Majalah Kedokteran Nusantara: The Journal of Medical School, 52(3), 95–102.

Nindrea, R. D., Usman, E., Katar, Y., Darma, I. Y., Warsiti, Hendriyani, H., & Sari, N. P. (2021). Dataset of Indonesian women’s reproductive, high-fat diet and body mass index risk factors for breast cancer. Data in Brief, 36. https://doi.org/10.1016/j.dib.2021.107107

Nishidono, Y., Saifudin, A., Nishizawa, M., Fujita, T., Nakamoto, M., & Tanaka, K. (2018). Identification of the chemical constituents in Ginger (Zingiber officinale) responsible for thermogenesis. Natural Product Communications, 13(7), 869–873. https://doi.org/10.1177/1934578x1801300722

Nur, Y., Cahyotomo, A., Nanda, N., & Fistoro, N. (2020). Profil GC-MS Senyawa Metabolit Sekunder dari Jahe Merah (Zingiber officinale) dengan Metode Ekstraksi Etil Asetat, Etanol dan Destilasi. Jurnal Sains Dan Kesehatan, 2(3), 198–204. https://doi.org/10.25026/jsk.v2i3.115

Prasetiyo, A. W. (2015). EKSTRAKSI OLEORESIN JAHE ( Zingiber officinale , Rosc .) DENGAN METODE EKSTRAKSI SOKLETASI ( Kajian Rasio Bahan Dengan Pelarut Dan Jumlah Sirkulasi Ekstraksi yang Paling Efisien). Jurnal Indrustria, 3(1), 2–9. https://doi.org/10.13140/RG.2.1.2361.8403

Seshadri VD, Oyouni AAA, Bawazir WM, Alsagaby SA, Alsharif KF, Albrakati A, A.-A. O. (2022). Zingiberene exerts chemopreventive activity against 7,12-dimethylbenz(a)anthracene-induced breast cancer in Sprague-Dawley rats. J Biochem Mol Toxicol.

Sidauruk, S. W., Ira Sari, N., Diharmi, A., & Arif, I. (2021). Aktivitas Antibakteri Ekstrak Sargassum plagyophyllum terhadap Bakteri Listeria monocytogenes dan Pseudomonas aeruginosa. Jurnal Pengolahan Hasil Perikanan Indonesia, 24(1), 27–37. https://doi.org/10.17844/jphpi.v24i1.33417

Situmorang, M., & Ricky, R. D. (2022). Identifikasi Senyawa Biokaktif Ekstrak Etanol dan Metanol Jahe Merah (Zingiber officinale var.Rubrum) dengan Menggunakan Gas Chromatography-Mass Spectrometer. Jurnal Ilmiiah Multi Disiplin Indonesia, 2(3), 528–539.

Supu, R. D., Diantini, A., & Levita, J. (2019). RED GINGER (Zingiber officinale var. rubrum): ITS CHEMICAL CONSTITUENTS, PHARMACOLOGICAL ACTIVITIES AND SAFETY. FITOFARMAKA: Jurnal Ilmiah Farmasi, 8(1), 23–29. https://doi.org/10.33751/jf.v8i1.1168

Tjendraputra, E.; Tran, V.H.; Liu-Brennan, D.; Roufogalis, B.D.; Duke, C. C. (2001). Effect of ginger constituents and synthetic analogues on cyclooxygenase-2 enzyme in intact cells. Bioorg. Chem, 29, 156–163.

Verenzia, N. A., Sukardi, S., & Wachid, M. (2022). Karakterisasi Fisikokimia dan Organoleptik Stik dengan Formulasi Tepung Lemon (Citrus limon L) dan Pati Jahe Merah (Zingiber officinale var Rubrum). Food Technology and Halal Science Journal, 5(1), 93–108. https://doi.org/10.22219/fths.v5i1.18979

Wakai, K., Dillon, D. S., Ohno, Y., Prihartono, J., Budiningsih, S., Ramli, M., Darwis, I., Tjindarbumi, D., Tjahjadi, G., Soetrisno, E., Roostini, E. S., Sakamoto, G., Herman, S., & Cornain, S. (2000). Fat intake and breast cancer risk in an area where fat intake is low: A case-control study in Indonesia. International Journal of Epidemiology, 29(1), 20–28. https://doi.org/10.1093/ije/29.1.20

Yuni Subhi Isnaini, Bahrah Bahrah, M. K. S. (2024). Kandungan Senyawa Aktif Jahe Merah Menggunakan Metode Kromatografi Gas–Spektrometri Massa (GC-MS). MAHESA: MALAHAYATI HEALTH STUDENT JOURNAL, 4, 3612–3627.

Zhang, Q. W., Lin, L. G., & Ye, W. C. (2018). Techniques for extraction and isolation of natural products: A comprehensive review. Chinese Medicine (United Kingdom), 13(1), 1–26. https://doi.org/10.1186/s13020-018-0177-x

Zhang, S., Kou, X., Zhao, H., Mak, K. K., Balijepalli, M. K., & Pichika, M. R. (2022). Zingiber officinale var. rubrum: Red Ginger’s Medicinal Uses. Molecules, 27(3). https://doi.org/10.3390/molecules27030775




DOI: https://doi.org/10.14421/biomedich.2025.142.1451-1458

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Copyright (c) 2025 Laili Nailul Muna, Enny Riyan Hasni, Farhatul Uyun, Erna Wulandari



Biology, Medicine, & Natural Product Chemistry
ISSN 2089-6514 (paper) - ISSN 2540-9328 (online)
Published by Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity.

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