Mangiferin induces apoptosis in human ovarian adenocarcinoma OVCAR3 cells via the regulation of Notch3
Open accessAbstract
Ovarian cancer is the most lethal gynecological malignancy in the world. Our previous studies showed that mangiferin, purified from plant source, possessed anti-neoplasm effect on human lung adenocarcinoma A549 cells. This study aimed to determine the apoptosis-inducing effect of mangiferin on human ovarian carcinoma OVCAR3 cells. By in vitro studies, we found mangiferin significantly inhibited viability of OVCAR3 cells, and remarkably increased the sensitivity of OVCAR3 cells to cisplatin. In addition, the activation of caspase-dependent apoptosis was observed in mangiferin treated ovarian cancer cells. Importantly, we observed an obviously downregulated Notch expression after mangiferin treatment, indicating the crucial role of Notch in mangiferin mediated apoptosis. In contrast, overexpression of Notch3 abrogated the apoptosis-inducing efficacy of mangiferin, further demonstrating that mangiferin induced apoptosis via Notch pathway. Furthermore, OVCAR3 cell xenograft models revealed that mangiferin treatment inhibited tumor growth and expanded survival of tumor xenograft mice. Based on these results, we concluded that mangiferin could significantly inhibit the proliferation and induce apoptosis in OVCAR3 cells. Our study also suggested the anti-neoplasm effect of mangiferin might be via the regulation of Notch3. Taken together, by targeting cell apoptosis pathways and enhancing the response to cisplatin treatment, mangiferin may represent a potential new drug for the treatment of human ovarian cancer.
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For PI3K/Akt, MGF changes Akt Thr308/Ser473 and downstream GSK3β and mTORC1, leading to reduced protein synthesis and survival signaling in tumor cells, whereas in metabolic tissues, they support GLUT4 translocation and glycogen synthesis.
“For PI3K/Akt, changes in Akt Thr308/Ser473, and downstream GSK3β and mTOR complex 1 lead to reduced protein synthesis and survival signaling in tumor cells, whereas in metabolic tissues, they support GLUT4 translocation and glycogen synthesis (16,47-54).”
From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [48]
The Results (page not provided) report that mangiferin decreased phosphorylation of Akt at Ser473 and mTOR at Ser2448 in OVCAR3 ovarian cancer cells; the Discussion links PI3K/Akt/mTOR inhibition to its antineoplastic effect. The paper does not establish changes at Akt Thr308 or in GSK3β, identify the mTOR complex as mTORC1, or report reduced protein synthesis. It also does not address GLUT4 translocation or glycogen synthesis in metabolic tissues. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCaspase-dependent apoptosis and downregulated Notch3 expression occur in mangiferin-treated human ovarian adenocarcinoma OVCAR3 cells.
“In addition, in-depth research into the underlying mechanisms of mangiferin successfully elucidated that caspase-dependent apoptosis and obviously downregulated Notch3 expression occurs in mangiferin-treated human ovarian adenocarcinoma OVCAR3 cells (63).”
From Mangiferin: An effective therapeutic agent against several disorders (Review) (2018) · cites this paper as [63]
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Duang, X.-Y., Wang, Q., Zhou, X.-D., & Huang, D.-M. (2011) · Medical Hypotheses · doi:10.1016/j.mehy.2010.11.029 · Cited by 45 · see citing works
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Cited by
Sorted by citations
Mangiferin: An effective therapeutic agent against several disorders (Review)
Du, S., Liu, H., Lei, T., Xie, X., Wang, H., He, X., Tong, R., & Wang, Y. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9529 · Cited by 139 · see citing works
“Our previous studies contributed to the understanding of the underling molecular mechanism of mangiferin in oncotherapy (55,62,63).”
Self-citationMorozkina, S. N., Nhung Vu, T. H., Generalova, Y. E., Snetkov, P. P., & Uspenskaya, M. V. (2021) · Biomolecules · doi:10.3390/biom11010079 · Cited by 82 · see citing works
Tang, Z., Lai, C., Luo, J., Ding, Y., Chen, Q., & Guan, Z. (2021) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22705 · Cited by 26 · see citing works
Sarfraz, M., Khan, A., Batiha, G. E.-S., Akhtar, M. F., Saleem, A., Ajiboye, B. O., Kamal, M., Ali, A., Alotaibi, N. M., Aaghaz, S., et al. (2023) · Cancers · doi:10.3390/cancers15164194 · Cited by 20 · see citing works
Mangiferin in human disease: Multifaceted mechanisms and applications (Review)
Dai, Y., Huang, Q., Tan, M., Wang, Z., Jiang, C., Liu, Z., Zhang, S., & Song, S. (2026) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2026.5736 · Cited by 3 · see citing works
- Authors
- Zou, B., Wang, H., Liu, Y., Qi, P., Lei, T., Sun, M., & Wang, Y.
- Affiliations
- Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (CN)
- University of Electronic Science and Technology of China (CN)
- Corresponding author
- Wang, Yi
- Venue
- Oncology Reports
- Publisher
- Spandidos Publications
- Published
- 2017-03
- Volume
- 38
- Issue
- 3
- Pages
- 1431-1441
- ISSN
- 1021-335X (ISSN-L)
- 1791-2431
- PMC
- PMC5549032
- OpenAlex
- W2735513656
- Cited by
- 40
- References
- 3
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 3 · 2019: 3 · 2018: 5
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Oncology Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Fonds National de la Recherche Luxembourg
- Comisión de Investigaciones Científicas
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Natural Compound Pharmacology Studies
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- mangiferin, ovarian adenocarcinoma, OVCAR-3 cells, apoptosis, Notch3, Notch signaling, cisplatin sensitivity, caspase-dependent apoptosis, tumor xenografts, anticancer natural products
- MeSH terms
- Receptor, Notch3, Adenocarcinoma, Animals, Cisplatin, Female, Humans, Ovarian Neoplasms, Gene Expression Regulation, Neoplastic, Apoptosis, Drug Resistance, Neoplasm, Xenograft Model Antitumor Assays, Xanthones, Cell Line, Tumor, Mice
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