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Apigenin suppresses PD-L1 expression in melanoma and host dendritic cells to elicit synergistic therapeutic effects
Open accessAbstract
BACKGROUND: The PD-L1/PD-1 pathway blockade-mediated immune therapy has shown promising efficacy in the treatment of multiple cancers including melanoma. The present study investigated the effects of the flavonoid apigenin on the PD-L1 expression and the tumorigenesis of melanoma. METHODS: The influence of flavonoids on melanoma cell growth and apoptosis was investigated using cell proliferation and flow cytometric analyses. The differential IFN-γ-induced PD-L1 expression and STAT1 activation were examined in curcumin and apigenin-treated melanoma cells using immunoblotting or immunofluorescence assays. The effects of flavonoid treatment on melanoma sensitivity towards T cells were investigated using Jurkat cell killing, cytotoxicity, cell viability, and IL-2 secretion assays. Melanoma xenograft mouse model was used to assess the impact of flavonoids on tumorigenesis in vivo. Human peripheral blood mononuclear cells were used to examine the influence of flavonoids on PD-L1 expression in dendritic cells and cytotoxicity of cocultured cytokine-induced killer cells by cell killing assays. RESULTS: Curcumin and apigenin showed growth-suppressive and pro-apoptotic effects on melanoma cells. The IFN-γ-induced PD-L1 upregulation was significantly inhibited by flavonoids, especially apigenin, with correlated reductions in STAT1 phosphorylation. Apigenin-treated A375 cells exhibited increased sensitivity towards T cell-mediated killing. Apigenin also strongly inhibited A375 melanoma xenograft growth in vivo, with enhanced T cell infiltration into tumor tissues. PD-L1 expression in dendritic cells was reduced by apigenin, which potentiated the cytotoxicity of cocultured cytokine-induced killer cells against melanoma cells. CONCLUSIONS: Apigenin restricted melanoma growth through multiple mechanisms, among which its suppression of PD-L1 expression exerted a dual effect via regulating both tumor and antigen presenting cells. Our findings provide novel insights into the anticancer effects of apigenin and might have potential clinical implications.
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In co-culture with Jurkat T cells, apigenin increases T lymphocyte proliferation and promotes their apoptosis in breast cancer and melanoma cells.
“This capacity to modulate PD‐L1 has been further confirmed in co-culture settings with Jurkat T cells, where apigenin was shown to not only increase T lymphocyte proliferation, but also promote their apoptosis in breast cancer (MDA‐MB‐468) and melanoma (A375) cells.259,260”
From Drug repurposing for cancer therapy (2024) · cites this paper as [260]
The Results section on T cell-mediated melanoma killing reports that apigenin increased Jurkat T cell-mediated killing of A375 cells and IL-2 secretion, but it does not report measuring T-cell proliferation. A separate Results section reports apoptosis in apigenin-treated A375 cells, not apoptosis in the Jurkat co-culture. This paper does not study the breast-cancer cell line; page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn specific breast cancer and melanoma cell lines, apigenin negates the upregulation of PD-L1 induced by IFN-γ.
“For example, in specific breast cancer (MDA‐MB‐468, SK‐BR‐3, and 4T1) and melanoma (A375, A2058, and RPMI‐7951) cell lines, apigenin has shown efficacy in negating the upregulation of PD‐L1, an effect induced by IFN‐γ.”
From Drug repurposing for cancer therapy (2024) · cites this paper as [260]
The Results section reports that apigenin attenuated IFN-γ-induced PD-L1 upregulation in the three named melanoma cell lines. The Discussion says this is consistent with earlier breast-cancer findings, but this paper does not report the claimed result for MDA-MB-468, SK-BR-3, or 4T1 cells. No page numbers are available in our copy. (LLM, conf=0.90)
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ResultDrug repurposing for cancer therapy
Xia, Y., Sun, M., Huang, H., & Jin, W.-L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01808-1 · Cited by 443
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“Similarly, apigenin also suppressed PD-L1 in vitro in melanoma cells and in host dendritic cells; this potentiated the cytotoxicity of cocultured cytokine-induced killer cells against melanoma cells [155].”
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“Our daily diets are rich in flavonoids, and apigenin is one of the most common flavonoids, with proved anticancer activity (Bhattacharya et al., 2018; Chang et al., 2018; Li et al., 2018; Xia et al., 2018; Xu et al., 2018).”
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“In vitro, treatment of human melanoma cells with curcumin and apigenin could inhibit the expression of PD-L1 on the surface of the cell, suggesting that curcumin and apigenin may be alternative treatments for immune checkpoint blockade (72).”
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“Treatment with apigenin prevented induction of PD-L1 by γ-interferon in several melanoma cell cultures in vitro, and enhanced infiltration of T lymphocytes in murine xenografts of these melanoma cells, while simultaneously suppressing expression of PD-L1 in dendritic cells [338].”
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“The findings from this in vitro study, which demonstrated significant increases in PD-L1 expression as well as in cell invasion upon treatment with IFN-γ in the oral cancer cell lines, HN6 and HN15 (Figure 5I,J), are thus in line with those of a previous study [33] that emphasized the significant role of PD-L1 in canc…”
ResultWang, Y.-K., Zeng, Y., Yang, W.-Y., Wang, X., & Jiang, J.-W. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155608 · Cited by 36
Apigenin in cancer therapy: Prevention of genomic instability and anticancer mechanisms
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“The mechanistic evaluations confirmed that the suppression of the IFN-γ/PD-L1 axis by apigenin had been mediated through the inhibition of signal transducer and activator of transcription 1 (STAT1) phosphorylation.(89) Apigenin also has the ability to limit the proliferation and recruitment of immunosuppressive cells…”
BackgroundRong, W., Wan, N.-Y., Zheng, X., Shi, G., Jiang, C.-H., Pan, K., Gao, M., Yin, Z.-Q., Gao, Z., & Zhang, J. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153867 · Cited by 36
Self-citationActive ingredients of traditional Chinese medicine for enhancing the effect of tumor immunotherapy
Yang, C., Li, D., Ko, C.-N., Wang, K., & Wang, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1133050 · Cited by 35
Fontana, F., Raimondi, M., Domizio, A. D., Moretti, R., Marelli, M., & Limonta, P. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.06.011 · Cited by 35
“Finally, apigenin boosted T cell immunity through downregulation of PD-L1 expression in dendritic cells [72].”
BackgroundDendritic Cells: Versatile Players in Renal Transplantation
Lin, J., Wang, H., Liu, C., Cheng, A., Deng, Q., Zhu, H., & Chen, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.654540 · Cited by 34
Kariagina, A., & Doseff, A. I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415753 · Cited by 34
“STAT Apigenin 5–60 μM Phospho-STAT1, IFNγinduced PD-L1 expression ↓ Human melanoma A375, A2058, RPMI-7951 cell lines [207]”
BackgroundInfluentialShen, C., Zhang, Z., Tian, Y., Li, F., Zhou, L., Jiang, W., Yang, L., Zhang, B., Wang, L., & Zhang, Y. (2021) · BMC Medicine · doi:10.1186/s12916-021-02161-8 · Cited by 39
“In addition to tumor cells, apigenin and curcumin also decreased PD-L1 expression on DCs, which augmented T cell activity [42].”
BackgroundSelf-citationRegulation of dietary polyphenols on cancer cell pyroptosis and the tumor immune microenvironment
Huang, X., Wang, Y., Yang, W., Dong, J., & Li, L. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.974896 · Cited by 35
“Like luteolin and apigenin, CUR can reduce STAT1 phosphorylation and inhibit IFNγ-induced PD-L1 up-regulation in A375 human melanoma cells in vitro (85).”
BackgroundLi, K., Wang, J., Xie, Y., Lu, Z. E., Sun, W., Wang, K., Liang, J., & Chen, X. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02575-5 · Cited by 31
“CUR effectively suppressed the IFN-γ-triggered elevation of PD-L1 by impeding STAT1 phosphorylation, thereby furnishing a mechanistic elucidation for its modulation of PD-L1 in melanoma cells [47].”
BackgroundSelf-citationFocaccetti, C., Palumbo, C., Benvenuto, M., Carrano, R., Melaiu, O., Nardozi, D., Angiolini, V., Lucarini, V., Kërpi, B., Masuelli, L., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010232 · Cited by 34
Immunopotentiation effects of apigenin on NK cell proliferation and killing pancreatic cancer cells
Feng, Y.-B., Chen, L., Chen, F.-X., Yang, Y., Chen, G.-H., Zhou, Z.-H., & Xu, C.-F. (2023) · International Journal of Immunopathology and Pharmacology · doi:10.1177/03946320231161174 · Cited by 30
“Apigenin, recognized as a kind of bioactive flavonoid, shows to possess various pharmacological activities, not only can restrict tumor growth through multiple mechanisms but also modulate immune cell function under different body conditions.(9,26,27) Martı́nez et al.”
BackgroundLasso, P., Gomez‐Cadena, A., Urueña, C. P., Donda, A., Martínez-Usatorre, A., Romero, P. J., Barreto, A., & Susana Fiorentino, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.584959 · Cited by 41
“A recent study showed that two polyphenolic compounds, curcumin and apigenin, decrease the PD-L1 expression on melanoma cells in vitro and in vivo in a murine model, diminishing the tumor growth and increasing immune cell infiltration (40).”
BackgroundYamagata, K., Uzu, E., Yoshigai, Y., Kato, C., & Tagami, M. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174116 · Cited by 29
Regulation of in vivo delivery of nanomedicines by herbal medicines
Guan, J., Chen, W., Yang, M., Wu, E., Qian, J., & Zhan, C. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.04.015 · Cited by 35
Regulation of Cancer Immune Checkpoints: Molecular and Cellular Mechanisms and Therapy
Xu, J. (2020) · doi:10.1007/978-981-15-3266-5 · Cited by 29
Li, R., Zhan, Y., Ding, X., Cui, J., Han, Y., Zhang, J., Zhang, J., Li, W., Wang, L., & Jiang, J. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.83599 · Cited by 26
“Also, p-STAT1 is a transcriptional factor that directly binds to PD-L1 promoter [43]; thus, inhibition of STAT1 phosphorylation by CGA might add extra suppression to the PD-L1 expression [44].”
BackgroundSelf-citationLiu, Z.-H., Wu, Y., Zhang, Y.-Q., Yuan, M.-L., Li, X.-L., Gao, J.-Y., Zhang, S., Xing, C.-J., Qin, H.-M., Zhao, H., et al. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01258 · Cited by 27
“Western Blot Analysis Proteins were extracted from cells, mouse tumor specimens, and frozen human gastric cancer specimens with RIPA lysis buffer as described previously (16).”
MethodSelf-citationPhytochemicals in regulating PD ‐1/ PD‐L1 and immune checkpoint blockade therapy
Zhong, C., Yang, C., Gao, X., Dong, J., & Zhong, C. (2023) · Phytotherapy Research · doi:10.1002/ptr.8082 · Cited by 30
“Xu et al. (2018) reported that curcumin abolished PD-L1 expression which was induced by IFN-γ in melanoma cells.”
BackgroundInfluentialRecent Advances in Phenolic Metabolites and Skin Cancer
Pop, T. D., & Diaconeasa, Z. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189707 · Cited by 34
“Flavonoids Subclass of Polyphenols Compound Sources Study Type Effect Cell Lines Ref Flavanols Catechin ((-)- epigallocatechin- 3-gallate (EGCG)) Green tea In vitro ↓ cell growth ↓ migration ↓ invasion SK-MEL 5 SK-MEL 28 A375 G361 [119] In vivo ↓ size and number of metastatic nodules Lung metastasis mouse B16-F10 In v…”
BackgroundRiemann, D., Schütte, W., Turzer, S., Seliger, B., & Möller, M. (2020) · Cancers · doi:10.3390/cancers12102966 · Cited by 28
“Whereas a negligible PD-L1/CD274 expression of blood pDC and mDC of healthy donors has been described [29], blood DC of lung cancer patients show a clear PD-L1/CD274 expression in this study, thereby confirming the data of blood DC in patients with ovarian cancer [2] and melanoma [30].”
ResultFlavonoid-based nanomedicines to target tumor microenvironment
Talib, W. H., Abuawad, A., Thiab, S. H., Alshweiat, A., & Mahmod, A. I. (2022) · OpenNano · doi:10.1016/j.onano.2022.100081 · Cited by 27
The immunoregulatory function of polyphenols: implications in cancer immunity
de Carvalho, J. T. G., Baldivia, D. D. S., de Castro, D. T. H., dos Santos, H. F., dos Santos, C. M., Oliveira, A. S., Monteiro‐Alfredo, T., Vilharva, K. N., Souza, K. D. P., & dos Santos, E. L. (2020) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2020.108428 · Cited by 27
Anticancer natural products targeting immune checkpoint protein network
Chun, K., Kim, D., Raut, P. K., & Surh, Y. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.11.006 · Cited by 24
The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells
Maruyama, T., Kobayashi, S., Nakatsukasa, H., Moritoki, Y., Taguchi, D., Sunagawa, Y., Morimoto, T., Asao, A., Jin, W., Owada, Y., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.687669 · Cited by 28
“Other studies have revealed that curcumin can suppress the interferon gamma (IFN-g)-induced upregulation of PD-L1 expression in cancer cells (56).”
BackgroundIsolation of DNA Aptamer Targeting PD-1 with an Antitumor Immunotherapy Effect.
Gao, T., & Pei, R. (2020) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c00919 · Cited by 23
Aronia melanocarpa Flavonol Extract—Antiradical and Immunomodulating Activities Analysis
Bushmeleva, K., Vyshtakalyuk, A., Terenzhev, D., Belov, T., Nikitin, E., & Zobov, V. (2023) · Plants · doi:10.3390/plants12162976 · Cited by 21
Phytochemicals as Immunomodulatory Agents in Melanoma
Tabolacci, C., Vita, D. D., Facchiano, A., Bozzuto, G., Beninati, S., Failla, C. M., Martile, M. D., Lintas, C., Mischiati, C., Stringaro, A., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032657 · Cited by 30
Apigenin and Temozolomide Synergistically Inhibit Glioma Growth Through the PI3K/AKT Pathway
Wang, D., Wang, Z., Dai, X.-D., Zhang, L., & Li, M. (2021) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/cbr.2020.4283 · Cited by 21
“18 Furthermore, API induces a strong inhibitory effect on glioma cell growth by promoting the expression of miR-16 and the suppression of Bcl2 and NF-j B/ Matrix Metallopeptidase 9 (MMP-9).”
Self-citationOršolić, N., Kunštić, M., Kukolj, M., Odeh, D., & Ančić, D. (2020) · Molecules · doi:10.3390/molecules25235583 · Cited by 29
“[36], IFN-γ acts as an important cytokine in the tumor microenvironment that can potently induce the expression of PD-L1 and indoleamine-2,3-dioxygenase (IDO) in cancer cells to contribute to tumor immune evasion.”
BackgroundTargeting the tumor immune microenvironment with “nutraceuticals”: From bench to clinical trials
Masuelli, L., Benvenuto, M., Focaccetti, C., Ciuffa, S., Fazi, S., Bei, A., Miele, M. T., Piredda, L., Manzari, V., Modesti, A., et al. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107700 · Cited by 22
Santana-Krímskaya, S. E., Franco-Molina, M. Á., Zárate-Triviño, D. G., Prado-Garcı́a, H., Zapata‐Benavides, P., Torres-del-Muro, F., & Rodrı́guez-Padilla, C. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110062 · Cited by 26
Mokhtari, R. B., Sambi, M., Qorri, B., Baluch, N., Ashayeri, N., Kumar, S., Cheng, H. M., Yeger, H., Das, B., & Szewczuk, M. R. (2021) · Cancers · doi:10.3390/cancers13143596 · Cited by 25
Ghiƫu, A., Pavel, I. Z., Avram, Ș., Kis, B., Minda, D., Dehelean, C., Buda, V., Folescu, R., & Danciu, C. (2021) · Analytical Cellular Pathology · doi:10.1155/2021/5552664 · Cited by 20
“The researchers showed that API (30μM) presented inhibitory effects on the expression levels of PD-L1 and stimulation of IFN-γ [31].”
BackgroundInfluentialTong, Q., & Wu, Z.-Q. (2023) · Clinical anatomy (New York, N.Y. Print) · doi:10.1002/ca.24057 · Cited by 19
“Curcumin, as a traditional Chinese medicine, has been demonstrated in earlier studies to regulate cell cycle regulators, inhibit tumor progression and control the growth of various solid malignancies by restraining immune responses (Hassanalilou et al., 2019; Zhang et al., 2018).”
BackgroundRecent insights into the biological functions of apigenin
Kim, J. K., & Park, S. (2020) · EXCLI Journal : Experimental and Clinical Sciences · doi:10.17179/excli2020-2579 · Cited by 19
“Xu et al., 2018 Both in vivo and in vitro trials of apigenin revealed that it can defend renal function against ischemia/reperfusion injury and also inhibit the growth of renal tubular cells from apoptosis through phosphoinositide 3-kinase (PI3K)/Akt mediated mitochondria-dependent apoptosis…”
Wang, W., Liu, X., Zhang, Z., Yin, M., Chen, X., Zhao, S., & Wu, L. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/8172866 · Cited by 15
“It was also found that apigenin suppresses PD-L1 expression in melanoma and host dendritic cells to elicit synergistic therapeutic e ff ects [28].”
Self-citationFocaccetti, C., Benvenuto, M., Ciuffa, S., Fazi, S., Scimeca, M., Nardi, A., Miele, M. T., Battisti, A., Bonanno, E., Modesti, A., et al. (2020) · Nutrients · doi:10.3390/nu12051417 · Cited by 16
“Treatment with CUR and API, in addition to inhibiting tumor growth of melanoma cells xenografted onto C57BL/6 mice, was able to inhibit IFN-γ-induced Programmed death-ligand (PD-L)1 expression and to enhance T-cell-mediated melanoma cell killing [48].”
BackgroundBreaking Immunosuppression to Enhance Cancer Stem Cell-Targeted Immunotherapy
Zheng, F., Zhang, S., Chang, A. E., Moon, J. J., Wicha, M. S., Wang, S. X., Chen, J., Liu, J.-X., Cheng, F.-J., & Li, Q. (2025) · International Journal on Biological Sciences · doi:10.7150/ijbs.101025 · Cited by 16
“Hence, anti-PD-L1 treatment blocking PD-L1 on both DCs and CSCs may explain the synergistic effects of DC vaccines combined with anti-PD-L1 treatment in mouse models [50, 51].”
Self-citationCai, S.-J., Gou, Y., Chen, Y., Hou, X., Zhang, J., Bi, C., Gu, P., Yang, M., Zhang, H.-X., Zhong, W., et al. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.18535 · Cited by 16
Self-citationZhang, M., Yang, L.-S., Wang, Y., Zuo, Y.-Z., Chen, D.-H., & Guo, X. (2023) · Scientific Reports · doi:10.1038/s41598-023-34238-0 · Cited by 16
Polyphenols: Chemoprevention and therapeutic potentials in hematological malignancies
Izuegbuna, O. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.1008893 · Cited by 17
Kurata, M., Fujiwara, N., Fujita, K., Yamanaka, Y., Seno, S., Kobayashi, H., Miyamae, Y., Takahashi, N., Shibuya, Y., & Masuda, S. (2019) · iScience · doi:10.1016/j.isci.2019.11.033 · Cited by 16
Potential anticancer effects and toxicity of flavones luteolin and apigenin in vivo
Li, X.-L., Li, Y., Chen, S., Guo, L., & Mei, N. (2025) · Journal of environmental science and health. Part C, Toxicology and carcinogenesis · doi:10.1080/26896583.2025.2527437 · Cited by 15
Advances in research on flavonoids in tumor immunotherapy (Review)
Yan, C., & Wang, G. (2025) · Molecular Medicine Reports · doi:10.3892/mmr.2025.13515 · Cited by 16
“At the concentration of 30 µM, apigenin decreases expression of PD‑L1, and this effect is associated with a decrease in STAT1 phosphoryla‑ tion (139,140).”
Afshari, A. R., Sanati, M., Ahmadi, S. S., Kesharwani, P., & Sahebkar, A. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216955 · Cited by 14
Aptamer-functionalized targeted siRNA delivery system for tumor immunotherapy
Lv, H., Wang, T., Ma, F., Zhang, K., Gao, T., Pei, R., & Zhang, Y. (2022) · Biomedical Materials · doi:10.1088/1748-605x/ac5415 · Cited by 23
“To verify this hypothesis, the T cells and tumor cells co-culture experiment was carried out as previously reported [39].”
Self-citationRecent advances of molecular mechanisms of regulating PD-L1 expression in melanoma
Han, J., Xu, X., Liu, Z., Li, Z., Wu, Y., & Zuo, D. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106971 · Cited by 16
Self-citationPolyphenols: Potential Applications in Cancer Therapy
Oriol‐Caballo, M., Moreno-Murciano, P., López‐Blanch, R., Estrela, J. M., & Obrador, E. (2025) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.70011 · Cited by 17
Wu, Y., Yin, M., Xia, W., Dou, B., Liu, X., & Sun, R. (2025) · Phytotherapy Research · doi:10.1002/ptr.8456 · Cited by 14
Self-citationAbdul-Razek, N., Khalil, R. G., Abdel‐Latif, M., Kamel, M. M., Alhazza, I. M., Awad, E. M., Ebaid, H., & Abuelsaad, A. S. A. (2024) · BioNanoScience · doi:10.1007/s12668-024-01767-5 · Cited by 12
“Several research studies have verified the PD-1/PD-L1 inhibitory effect of flavonoids via cell-based and in vitro studies [105, 106].”
Polyphenols targeting multiple molecular targets and pathways for the treatment of vitiligo
Yang, Y.-X., Du, Y.-Y., & Cui, B. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1387329 · Cited by 14
Sun, Z.-O., Yin, S.-T., Zhao, C., Fan, L., & Hu, H. (2022) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2022.05.082 · Cited by 14
Hu, W., Ma, Y.-R., Zhao, C., Yin, S.-T., & Hu, H. (2021) · Molecular Carcinogenesis · doi:10.1002/mc.23340 · Cited by 14
Herbal Medicines Attenuate PD-L1 Expression to Induce Anti-Proliferation in Obesity-Related Cancers
Yang, Y. S. H., Li, Z., Shih, Y.-J., Bennett, J. A., Whang-Peng, J., Lin, H., Davis, P. J., & Wang, K. (2019) · Nutrients · doi:10.3390/nu11122979 · Cited by 16
“A combination of curcumin and apigenin suppresses cancer cell growth and induces pro-apoptotic effects in melanoma cells [67].”
BackgroundHsieh, T., & WU, J. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20235969 · Cited by 12
“Apigenin: human melanoma & dendritic cells 30 μM apigenin more effective than curcumin in inhibiting IFNγ (10 ng/mL) mediated induction of PD-L1 in melanoma cells tested; apigenin highly effective in inhibiting IFN-γ (1000 U/mL) mediated induction of PD-L1 in PBMC-derived dendritic cells from healthy volunteers [34]”
BackgroundInfluentialReytor-González, C., Jiménez-Flores, E., Gonzalez, N. L., & Simancas‐Racines, D. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26168037 · Cited by 17
“Additionally, curcumin disrupts STAT3 activation by preventing its phosphorylation and DNA-binding activity, suppressing the expression of survival genes like Mcl-1, X-linked inhibitor of apoptosis protein gene, and PD-L1 [143–145].”
T cell dysregulation in rheumatoid arthritis: Recent advances and natural product interventions
Hu, M., Zhou, Y., Yao, Z., Tang, Y., Zhang, Y., Liao, J., Cai, X., & Liu, L. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114499 · Cited by 14
Self-citationLysosome-Targeting Chimera Using Mannose-6-Phosphate Glycans Derived from Glyco-Engineered Yeast
Kim, S., Kang, J., An, D., Seo, J., & Oh, D. (2025) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.4c00512 · Cited by 14
Apigenin inhibits tumor angiogenesis by hindering microvesicle biogenesis via ARHGEF1.
Zhang, W., Zhuang, X., Wu, C., Jin, Y., Xing, J., Hou, M., Yang, W., Feng, Q.-Y., & Wang, H. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216961 · Cited by 13
Metadata
- Authors
- Xu, L., Zhang, Y., Tian, K., Chen, X., Zhang, R., Mu, X., Wu, Y., Wang, D., Wang, S., Liu, F., Wang, T., Zhang, J., Liu, S., Zhang, Y., Tu, C., & Liu, H.
- Affiliations
- Dalian Medical University (CN)
- Corresponding author
- Liu, Han
- ORCID
- Venue
- Journal of Experimental & Clinical Cancer Research
- Published
- 2018-10-29
- Volume
- 37
- Issue
- 1
- Pages
- 261-261
- ISSN
- 0392-9078 (ISSN-L)
- 1756-9966
- PMC
- PMC6206930
- OpenAlex
- W2898843431
- Cited by
- 177
- References
- 47
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 29 · 2023: 24 · 2022: 26 · 2021: 30 · 2020: 22 · 2019: 12
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Experimental & Clinical Cancer Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81273921, 81601901, 81301901)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- apigenin, melanoma, PD-L1 expression, PD-1/PD-L1 pathway, flavonoids, curcumin, STAT1 phosphorylation, interferon-gamma, apoptosis, T cell cytotoxicity, dendritic cells, cytokine-induced killer cells, tumor xenografts, tumor immune microenvironment, anticancer agents
- MeSH terms
- Animals, Cell Survival, Curcumin, Dendritic Cells, Humans, Interferon-gamma, Interleukin-2, Melanoma, T-Lymphocytes, Down-Regulation, Gene Expression Regulation, Neoplastic, Coculture Techniques, Jurkat Cells, Xenograft Model Antitumor Assays, Cell Line, Tumor, Apigenin, Cell Proliferation, Mice, B7-H1 Antigen
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