Anticancer Effectivity of Nanocrystals Derived from Mangosteen (Garcinia mangostana) Peel Extract on Leukemia HL-60 Cells
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Keywords:
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Anticancer, Garcinia mangostana, HL-60 Cells, Leukemia, Nanocrystal
Abstract
Leukemia, characterized by abnormal leukocyte proliferation, ranks ninth in Indonesia as the most common cancer. While treatments such as chemotherapy and radiation effectively target cancer cells, they also risk damaging healthy blood cells. This has spurred interest in exploring low-toxicity herbal compounds as potential therapies, with mangosteen peel emerging as a widely researched option. Nanotechnology, which has the potential to enhance the bioavailability of herbal compounds, is also a focus of extensive research. This study objective was to assess the impact of Mangosteen Peel Nanocrystal (MPN) on HL-60 leukemia cells by analyzing various parameters, including cytotoxicity, reactive oxygen species (ROS) levels, senescence, and gene expression changes. MPN was prepared with high-speed milling and characterized using particle size analyzers, microscopy, and stability assessments. HL-60 cells were cultured and subjected to MPN treatment. Cytotoxicity was evaluated using WST-8 assays, ROS levels were assessed using flow cytometry, and senescence analyses using Senescence-Associated b-Galactosidase Staining. AKT and FLT-1 gene expression were determined via qRT-PCR. MPN has been successfully characterized as a nanoparticle based on size, stability, and morphology. MPN has an impact on leukemia cells by increasing cytotoxicity, decreasing ROS levels, inducing senescence, and modulating AKT and FLT-1 gene expressions. The findings suggest potential implications for MPN in targeting leukemia cells. The study sheds light on the promising effects of MPN in leukemia cell models, indicating its potential applications in targeting cancer cells, inducing senescence, decreasing ROS levels, and modulating gene expressions related to cell survival and proliferation.
References
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Grover, I. S., S. Singh, and B. Pal (2013). The Preparation, Surface Structure, Zeta Potential, Surface Charge Density and Photocatalytic Activity of TiO2 Nanostructures of Different Shapes. Applied Surface Science, 280; 366–372
Guo, M., S. Qin, S. Wang, M. Sun, H. Yang, and X. Wang (2023). Herbal Medicine Nanocrystals: A Potential Novel Therapeutic Strategy. Molecules, 28; 6370
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López-García, J., M. Lehocký, P. Humpolíček, and P. Sáha (2014). HaCaT Keratinocytes Response on Antimicrobial Atelocollagen Substrates: Extent of Cytotoxicity, Cell Viability, and Proliferation. Journal of Functional Biomaterials, 5; 43–57
Ma, L., Z. Xu, J. Wang, Z. Zhu, G. Lin, and L. Jiang (2017). Matrine Inhibits BCR/ABL Mediated ERK/MAPK Pathway in Human Leukemia Cells. Oncotarget, 8; 108880
Maher, T., R. Raus, D. Daddiouaissa, F. Ahmad, N. Adzhar, E. Latif, F. Abdulhafiz, and A. Mohammed (2021). Medicinal Plants with Anti-Leukemic Effects: A Review. Molecules, 26; 2741
Markowicz, J., Ł. Uram, J. Sobich, L. Mangiardi, P. Maj, and W. Rode (2019). Antitumor and Anti-Nematode Activities of ????-Mangostin. European Journal of Pharmacology, 863; 172678
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McGuckin, M., J. Wang, R. Ghanma, N. Qin, S. Palma, and R. Donnelly (2022). Nanocrystals as a Master Key to Deliver Hydrophobic Drugs via Multiple Administration Routes. Journal of Controlled Release, 345; 334–353
Meylina, L., M. Muchtaridi, I. Joni, A. Mohammed, and N. Wathoni (2021). Nanoformulations of ????-Mangostin for Cancer Drug Delivery System. Pharmaceutics, 13; 1–21
Minute, L., A. Teijeira, A. Sanchez-Paulete, M. Ochoa, M. Alvarez, and I. Otano (2020). Cellular Cytotoxicity Is a Form of Immunogenic Cell Death. Journal of Immunotherapy for Cancer, 8; 1–14
Nagavarma, B., H. Yadav, A. Ayaz, L. Vasudha, and H. Shivakumar (2012). Different Techniques for Preparation of Polymeric Nanoparticles: A Review. Asian Journal of Pharmaceutical and Clinical Research, 5; 16–23
Nauman, M. and J. Johnson (2022). The Purple Mangosteen (Garcinia mangostana): Defining the Anticancer Potential of Selected Xanthones. Pharmaceutical Research, 175; 106032
Nepstad, I., K. J. Hatfield, I. S. Grønningsæter, and H. Reikvam (2020). The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells. International Journal of Molecular Sciences, 21; 2907
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Priyandoko, D., W. Widowati, and K. Y. Gunawan (2019). Ethanolic Extract of Moringa’s Leaves (Moringa oleifera) Induce Senescence on Adenocarcinomic Alveolar Basal Epithelial Cells (A549 Cell Lines). Proceeding of International Conference on Science, Health, and Technology; 156–159
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Rizaldy, D., R. Hartati, T. Nadhifa, and I. Fidrianny (2021). Chemical Compounds and Pharmacological Activities of Mangosteen (Garcinia mangostana L.): Updated Review. Biointerface Research in Applied Chemistry, 12; 2503–2516
Rusman, J. R., S. A. Sundari, A. Nuriliani, and H. T. Saragih (2021). Ameliorative Effect of Mangosteen (Garcinia mangostana L.) Peel Infusion on the Histopathological Structures of the Liver and Kidney of Rats (Rattus norvegicus Berkenhout, 1769) After H2O2 Induction. Veterinary World, 14; 1579
Sarmiento-Salinas, F. L., A. Perez-Gonzalez, A. Acosta-Casique, A. Ix-Ballote, A. Diaz, and S. Trevino (2021). Reactive Oxygen Species: Role in Carcinogenesis, Cancer Cell Signaling, and Tumor Progression. Life Sciences, 284; 119942
Sheng, X., J. Li, C. Zhang, L. Zhao, L. Guo, and T. Xu (2019). ????-Mangostin Promotes Apoptosis of Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Reactive Oxygen Species-Dependent Activation of ERK1/2 Mitogen-Activated Protein Kinase. Journal of Cellular Biochemistry, 120; 14986–14994
Subramanian, D. A., R. Langer, and G. Traverso (2022). Mucus Interaction to Improve Gastrointestinal Retention and Pharmacokinetics of Orally Administered Nano-Drug Delivery Systems. Journal of Nanobiotechnology, 20; 1–23
Verma, N., S. Pandit, A. Kumar, G. Yadav, S. K. Giri, and D. Lahiri (2022). Recent Update on Active Biological Molecules in Generating the Anticancerous Therapeutic Potential of Garcinia Mangostana. Applied Biochemistry and Biotechnology, 194; 4724–4744
Wang, W., B. Zhang, Y. Shi, D. Zhou, and R. Wang (2022). Improvement in Dispersion Stability of Alumina Suspensions and Corresponding Chemical Mechanical Polishing Performance. Applied Surface Science, 597; 153703
Wang, Y., H. Mo, J. Gu, K. Chen, Z. Han, and Y. Liu (2017). Cordycepin Induces Apoptosis of Human Acute Monocytic Leukemia Cells via Downregulation of the ERK/Akt Signaling Pathway. Experimental and Therapeutic Medicine, 14; 3067–3073
Widowati, W., L. Darsono, J. Suherman, Y. Yelliantty, and M. Maesaroh (2014). High Performance Liquid Chromatography (HPLC) Analysis, Antioxidant, Antiaggregation of Mangosteen Peel Extract (Garcinia mangostana L.). International Journal of Bioscience, Biochemistry, and Bioinformatics, 4; 458
Widowati, W., D. Priyandoko, L. Lenny, R. Revika, S. Novianti, and H. S. W. e. a. Kusuma (2024). Camellia sinensis L. Extract Suppresses Inflammation on Acute Respiratory Distress Syndrome Cells Models via Decreasing IL-1???? , IL-6, and COX-2 Expressions. Trends in Sciences, 21; 7010
Widowati, W., T. L. Wargasetia, V. Kurniawati, R. Rachmaniar, V. A. Yuninda, and A. H. Sabrina (2023). In-Vitro Study of Potential Antioxidant Activities of Mangosteen and Its Nanoemulsions. Medicinal Plants-International Journal of Phytomedicine, 15; 534–542
Xia, J., M. Wang, Y. Zhu, C. Bu, and T. Li (2022). Differential mRNA and Long Noncoding RNA Expression Profiles in Pediatric B-Cell Acute Lymphoblastic Leukemia Patients. BMC Pediatrics, 22; 1–11
Xiu, B., W. Zhang, B. Huang, J. Chen, H. Lu, and J. Fu (2018). Genetic Inhibition of Vascular Endothelial Growth Factor Receptor-1 Significantly Inhibits the Migration and Proliferation of Leukemia Cells and Increases Their Sensitivity to Chemotherapy. Oncology Reports, 29; 2030–2038
Yenurkar, D., M. Nayak, and S. Mukherjee (2023). Recent Advances of Nanocrystals in Cancer Theranostics. Nanoscale Advances, 5; 4018–4040
Yu, T., X. Huang, J. Liu, Q. Fu, B. Wang, and Z. Qian (2019). Polymeric Nanoparticles Encapsulating alpha-Mangostin Inhibit the Growth and Metastasis in Colorectal Cancer. Applied Materials Today, 16; 351–366
Arti, S., M. Bharti, V. Kumar, V. Rehani, and J. Dhiman (2022). Drug Nanocrystals as Nanocarrier-Based Drug Delivery Systems. Industrial Applications of Nanocrystals, 16; 179–203
Aslantürk, O. (2018). In Vitro Cytotoxicity and Cell Viability Assays: Principles, Advantages, and Disadvantages. Genotoxicity–A Predictable Risk to Our Actual World, 2; 64–80
Boinpelly, V., R. Verma, S. Srivastav, R. Srivastava, and S. Shankar (2020). ????-Mangostin-Encapsulated PLGA Nanoparticles Inhibit Colorectal Cancer Growth by Inhibiting Notch Pathway. Journal of Cellular and Molecular Medicine, 24; 11343–11354
Chamchoy, K., D. Pakotiprapha, P. Pumirat, U. Leartsakulpanich, and U. Boonyuen (2019). Application of WST-8 Based Colorimetric NAD(P)H Detection for Quantitative Dehydrogenase Assays. BMC Biochemistry, 20; 1–14
Dong, Y., O. Shi, Q. Zeng, X. Lu, W. Wang, and Y. Li (2020). Leukemia Incidence Trends at the Global, Regional, and National Level Between 1990 and 2017. Experimental Hematology & Oncology, 9; 1–11
Fakhri, S., S. Moradi, L. DeLiberto, and A. Bishayee (2022). Cellular Senescence Signaling in Cancer: A Novel Therapeutic Target to Combat Human Malignancies. Biochemical Pharmacology, 199; 114989
Garg, P., R. Garg, D. Horne, S. Awasthi, R. Salgia, and S. Singhal (2023). Prognostic Significance of Natural Products Against Multidrug Tumor Resistance. Cancer Letters, 557; 216079
Garniasih, D., S. Susanah, Y. Sribudiani, and D. Hilmanto (2020). The Incidence and Mortality of Childhood Acute Lymphoblastic Leukemia in Indonesia: A Systematic Review and Meta-Analysis. PLoS ONE, 17; e0269706
Girsang, E., C. N. Ginting, I. N. Lister, K. Y. Gunawan, and W. Widowati (2021). Anti-Inflammatory and Antiaging Properties of Chlorogenic Acid on UV-Induced Fibroblast Cell. PeerJ, 9; e11419
Gondokesumo, M. E. (2019). Xanthones Analysis and Antioxidant Activity Analysis (Applying ESR) of Six Different Maturity Levels of Mangosteen Rind Extract (Garcinia mangostana Linn.). Pharmacognosy Journal, 11; 369–373
Grover, I. S., S. Singh, and B. Pal (2013). The Preparation, Surface Structure, Zeta Potential, Surface Charge Density and Photocatalytic Activity of TiO2 Nanostructures of Different Shapes. Applied Surface Science, 280; 366–372
Guo, M., S. Qin, S. Wang, M. Sun, H. Yang, and X. Wang (2023). Herbal Medicine Nanocrystals: A Potential Novel Therapeutic Strategy. Molecules, 28; 6370
Harlisa, P., H. K. Sentono, B. Purwanto, and P. Dirgahayu (2022). The Ethyl Acetate Extract of Mangosteen Peel Cream Attenuates Ultraviolet B Radiation-Induced Apoptotic Cell Death Via Antioxidant Effect by Regulation TNF-???? and Caspase 3 in Guinea Pig Skin. Bangladesh Journal of Medical Science, 21; 512–520
Herdiana, Y., N. Wathoni, S. Shamsuddin, and M. Muchtaridi (2021). ????-Mangostin Nanoparticles Cytotoxicity and Cell Death Modalities in Breast Cancer Cell Lines. Molecules, 26; 5119
Huang, M., J. J. Lu, and J. Ding (2020). Natural Products in Cancer Therapy: Past, Present and Future. Natural Products and Bioprospecting, 11; 5–13
Joshi, K., A. Chandra, K. Jain, and S. Talegaonkar (2019). Nanocrystalization: An Emerging Technology to Enhance the Bioavailability of Poorly Soluble Drugs. Pharmaceutical Nanotechnology, 7; 259–278
Kalick, L. S., H. A. Khan, E. Maung, Y. Baez, A. N. Atkinson, and C. E. Wallace (2023). Mangosteen for Malignancy Prevention and Intervention: Current Evidence, Molecular Mechanisms, and Future Perspectives. Pharmaceutical Research, 188; 106630
Kato, C., M. Itaya-Takahashi, T. Miyazawa, J. Ito, I. S. Parida, and H. Yamada (2023). Effects of Particle Size of Curcumin Solid Dispersions on Bioavailability and Anti-Inflammatory Activities. Antioxidants, 12; 724
Kaur, G., A. Singh, and B. N. Dar (2020). Mangosteen (Garcinia mangostana L.). In G. A. Nayik and A. Gull, editors, Antioxidants in Fruits: Properties and Health Benefits. Springer, Singapore
Kurniawan, Y., K. Priyangga, Jumina, H. Pranowo, E. Sholikhah, and A. Zulkarnain (2021). An Update on the Anticancer Activity of Xanthone Derivatives: A Review. Pharmaceuticals, 1; 1144
Liana, L., R. Rizal, W. Widowati, F. Fioni, K. Akbar, E. Fachrial, and I. Lister (2019). Antioxidant and Anti-Hyaluronidase Activities of Dragon Fruit Peel Extract and Kaempferol-3-O-Rutinoside. Jurnal Kedokteran Brawijaya, 30; 247–252
López-García, J., M. Lehocký, P. Humpolíček, and P. Sáha (2014). HaCaT Keratinocytes Response on Antimicrobial Atelocollagen Substrates: Extent of Cytotoxicity, Cell Viability, and Proliferation. Journal of Functional Biomaterials, 5; 43–57
Ma, L., Z. Xu, J. Wang, Z. Zhu, G. Lin, and L. Jiang (2017). Matrine Inhibits BCR/ABL Mediated ERK/MAPK Pathway in Human Leukemia Cells. Oncotarget, 8; 108880
Maher, T., R. Raus, D. Daddiouaissa, F. Ahmad, N. Adzhar, E. Latif, F. Abdulhafiz, and A. Mohammed (2021). Medicinal Plants with Anti-Leukemic Effects: A Review. Molecules, 26; 2741
Markowicz, J., Ł. Uram, J. Sobich, L. Mangiardi, P. Maj, and W. Rode (2019). Antitumor and Anti-Nematode Activities of ????-Mangostin. European Journal of Pharmacology, 863; 172678
Matsumoto, K., Y. Akao, E. Kobayashi, K. Ohguchi, T. Ito, and T. Tanaka (2003). Induction of Apoptosis by Xanthones from Mangosteen in Human Leukemia Cell Lines. Journal of Natural Products, 66; 1124–1127
McGuckin, M., J. Wang, R. Ghanma, N. Qin, S. Palma, and R. Donnelly (2022). Nanocrystals as a Master Key to Deliver Hydrophobic Drugs via Multiple Administration Routes. Journal of Controlled Release, 345; 334–353
Meylina, L., M. Muchtaridi, I. Joni, A. Mohammed, and N. Wathoni (2021). Nanoformulations of ????-Mangostin for Cancer Drug Delivery System. Pharmaceutics, 13; 1–21
Minute, L., A. Teijeira, A. Sanchez-Paulete, M. Ochoa, M. Alvarez, and I. Otano (2020). Cellular Cytotoxicity Is a Form of Immunogenic Cell Death. Journal of Immunotherapy for Cancer, 8; 1–14
Nagavarma, B., H. Yadav, A. Ayaz, L. Vasudha, and H. Shivakumar (2012). Different Techniques for Preparation of Polymeric Nanoparticles: A Review. Asian Journal of Pharmaceutical and Clinical Research, 5; 16–23
Nauman, M. and J. Johnson (2022). The Purple Mangosteen (Garcinia mangostana): Defining the Anticancer Potential of Selected Xanthones. Pharmaceutical Research, 175; 106032
Nepstad, I., K. J. Hatfield, I. S. Grønningsæter, and H. Reikvam (2020). The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells. International Journal of Molecular Sciences, 21; 2907
Novilla, A., D. S. Djamhuri, N. Fauziah, M. Maesaroh, B. Balqis, and W. Widowati (2016). Cytotoxic Activity of Mangosteen (Garcinia mangostana L.) Peel Extract and ????-Mangostin Toward Leukemia Cell Lines (HL-60 and K-562). Journal of Natural Remedies, 16; 52–59
Nugroho, D., D. Daratika, E. Agustin, M. Kamila, M. Rifada, and L. Togatorop (2019). Characteristic of Garcinia mangostana’s Pericarp Prepared by Mechanical Milling. In Proceedings of the 16th ASEAN Food Conference. Bali, Indonesia, pages 15–18
Priyandoko, D., W. Widowati, and K. Y. Gunawan (2019). Ethanolic Extract of Moringa’s Leaves (Moringa oleifera) Induce Senescence on Adenocarcinomic Alveolar Basal Epithelial Cells (A549 Cell Lines). Proceeding of International Conference on Science, Health, and Technology; 156–159
Priyandoko, D., W. Widowati, W. Widodo, K. Kusdianti, H. Hernawati, and W. S. Widodo (2022). The Potential of Moringa oleifera Leaf Ethanolic Extract as Anticancer Against Lung Adenocarcinoma (A549) Cells and Its Toxicity on Normal Mammary Cells (MCF-12A). Trends in Sciences, 19; 3202
Rizaldy, D., R. Hartati, T. Nadhifa, and I. Fidrianny (2021). Chemical Compounds and Pharmacological Activities of Mangosteen (Garcinia mangostana L.): Updated Review. Biointerface Research in Applied Chemistry, 12; 2503–2516
Rusman, J. R., S. A. Sundari, A. Nuriliani, and H. T. Saragih (2021). Ameliorative Effect of Mangosteen (Garcinia mangostana L.) Peel Infusion on the Histopathological Structures of the Liver and Kidney of Rats (Rattus norvegicus Berkenhout, 1769) After H2O2 Induction. Veterinary World, 14; 1579
Sarmiento-Salinas, F. L., A. Perez-Gonzalez, A. Acosta-Casique, A. Ix-Ballote, A. Diaz, and S. Trevino (2021). Reactive Oxygen Species: Role in Carcinogenesis, Cancer Cell Signaling, and Tumor Progression. Life Sciences, 284; 119942
Sheng, X., J. Li, C. Zhang, L. Zhao, L. Guo, and T. Xu (2019). ????-Mangostin Promotes Apoptosis of Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Reactive Oxygen Species-Dependent Activation of ERK1/2 Mitogen-Activated Protein Kinase. Journal of Cellular Biochemistry, 120; 14986–14994
Subramanian, D. A., R. Langer, and G. Traverso (2022). Mucus Interaction to Improve Gastrointestinal Retention and Pharmacokinetics of Orally Administered Nano-Drug Delivery Systems. Journal of Nanobiotechnology, 20; 1–23
Verma, N., S. Pandit, A. Kumar, G. Yadav, S. K. Giri, and D. Lahiri (2022). Recent Update on Active Biological Molecules in Generating the Anticancerous Therapeutic Potential of Garcinia Mangostana. Applied Biochemistry and Biotechnology, 194; 4724–4744
Wang, W., B. Zhang, Y. Shi, D. Zhou, and R. Wang (2022). Improvement in Dispersion Stability of Alumina Suspensions and Corresponding Chemical Mechanical Polishing Performance. Applied Surface Science, 597; 153703
Wang, Y., H. Mo, J. Gu, K. Chen, Z. Han, and Y. Liu (2017). Cordycepin Induces Apoptosis of Human Acute Monocytic Leukemia Cells via Downregulation of the ERK/Akt Signaling Pathway. Experimental and Therapeutic Medicine, 14; 3067–3073
Widowati, W., L. Darsono, J. Suherman, Y. Yelliantty, and M. Maesaroh (2014). High Performance Liquid Chromatography (HPLC) Analysis, Antioxidant, Antiaggregation of Mangosteen Peel Extract (Garcinia mangostana L.). International Journal of Bioscience, Biochemistry, and Bioinformatics, 4; 458
Widowati, W., D. Priyandoko, L. Lenny, R. Revika, S. Novianti, and H. S. W. e. a. Kusuma (2024). Camellia sinensis L. Extract Suppresses Inflammation on Acute Respiratory Distress Syndrome Cells Models via Decreasing IL-1???? , IL-6, and COX-2 Expressions. Trends in Sciences, 21; 7010
Widowati, W., T. L. Wargasetia, V. Kurniawati, R. Rachmaniar, V. A. Yuninda, and A. H. Sabrina (2023). In-Vitro Study of Potential Antioxidant Activities of Mangosteen and Its Nanoemulsions. Medicinal Plants-International Journal of Phytomedicine, 15; 534–542
Xia, J., M. Wang, Y. Zhu, C. Bu, and T. Li (2022). Differential mRNA and Long Noncoding RNA Expression Profiles in Pediatric B-Cell Acute Lymphoblastic Leukemia Patients. BMC Pediatrics, 22; 1–11
Xiu, B., W. Zhang, B. Huang, J. Chen, H. Lu, and J. Fu (2018). Genetic Inhibition of Vascular Endothelial Growth Factor Receptor-1 Significantly Inhibits the Migration and Proliferation of Leukemia Cells and Increases Their Sensitivity to Chemotherapy. Oncology Reports, 29; 2030–2038
Yenurkar, D., M. Nayak, and S. Mukherjee (2023). Recent Advances of Nanocrystals in Cancer Theranostics. Nanoscale Advances, 5; 4018–4040
Yu, T., X. Huang, J. Liu, Q. Fu, B. Wang, and Z. Qian (2019). Polymeric Nanoparticles Encapsulating alpha-Mangostin Inhibit the Growth and Metastasis in Colorectal Cancer. Applied Materials Today, 16; 351–366
Authors
Gondokesumo, M. E. ., Novilla, A., Prahastuti, S., Kusuma, H. S. W., Widowati, W., Zahiroh, F. H. ., Hadiprasetyo, D. S., & Surakusumah, W. (2025). Anticancer Effectivity of Nanocrystals Derived from Mangosteen (Garcinia mangostana) Peel Extract on Leukemia HL-60 Cells. Science and Technology Indonesia, 10(1), 228–237. https://doi.org/10.26554/sti.2025.10.1.228-237
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