Icaritin Exacerbates Mitophagy and Synergizes with Doxorubicin to Induce Immunogenic Cell Death in Hepatocellular Carcinoma

Yu, Zhuo; Guo, Jianfeng; Hu, Mengying; Gao, Yueqiu; Huang, Leaf

doi:10.1021/acsnano.0c00708

Cited by 262 publications

(184 citation statements)

References 40 publications

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“…On the one hand, inhibition of the mitophagic axis enhances tumor necrosis factor-based immunotherapy to control the survival and progression of cervical and gastric cancer cells (Yan et al, 2018;Zhao et al, 2019). On the other hand, enhanced mitophagy may induce immunogenic cell death, thereby inhibiting tumor growth through the activation of cytotoxic T lymphocytes in liver cancer cells (Yu et al, 2020). These findings further support that mitophagy may be an effective target for modified tumor immunotherapy.…”

Section: Mitophagy and Tumor Therapiesmentioning

confidence: 60%

Mitophagy Receptors in Tumor Biology

Xie

Liu

Kang

et al. 2020

Front. Cell Dev. Biol.

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Mitochondria are multifunctional organelles that regulate cancer biology by synthesizing macromolecules, producing energy, and regulating cell death. The understanding of mitochondrial morphology, function, biogenesis, fission and fusion kinetics, and degradation is important for the development of new anticancer strategies. Mitophagy is a type of selective autophagy that can degrade damaged mitochondria under various environmental stresses, especially oxidative damage and hypoxia. The key regulator of mitophagy is the autophagy receptor, which recognizes damaged mitochondria and allows them to enter autophagosomes by binding to MAP1LC3 or GABARAP, and then undergo lysosomal-dependent degradation. Many components of mitochondria, including mitochondrial membrane proteins (e.g., PINK1, BNIP3L, BNIP3, FUNDC1, NIPSNAP1, NIPSNAP2, BCL2L13, PHB2, and FKBP8) and lipids (e.g., cardiolipin and ceramides), act as mitophagy receptors in a context-dependent manner. Dysfunctional mitophagy not only inhibits, but also promotes, tumorigenesis. Similarly, mitophagy plays a dual role in chemotherapy, radiotherapy, and immunotherapy. In this review, we summarize the latest advances in the mechanisms of mitophagy and highlight the pathological role of mitophagy receptors in tumorigenesis and treatment.

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Section: Mitophagy and Tumor Therapiesmentioning

confidence: 60%

Mitophagy Receptors in Tumor Biology

Xie

Liu

Kang

et al. 2020

Front. Cell Dev. Biol.

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“…The late apoptotic release of nucleus‐localizing high mobility group box 1 (HMGB1) binds TLR2 and TLR4 on DCs, stimulates pro‐inflammatory cytokines production, and induces DCs maturation. [ 54 ] For the untreated cells or cells incubated with nanosheets alone, HMGB1 was mostly located in cell nuclei. A significant translocation of HMGB1 from nuclei to the extracellular milieu was observed in the cells following nanosheets plus NIR treatment (Figure 2f).…”

Section: Resultsmentioning

confidence: 99%

Reversing Immunosuppression in Hypoxic and Immune‐Cold Tumors with Ultrathin Oxygen Self‐Supplementing Polymer Nanosheets under Near Infrared Light Irradiation

Jiang

Wang

et al. 2021

Adv Funct Materials

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Solid tumors are characterized by a hypoxic and immunologically “cold” microenvironment that dramatically limits the therapeutic outcomes of immunotherapy. Thus, strategies and materials that are capable of reversing immunosuppression in immune‐cold tumors are highly desired. Herein, it is reported that oxygen (O2) self‐supplementing conjugated microporous polymer nanosheets can be utilized to elicit a robust antitumor T cell immune response in the hypoxic and immunosuppressive tumor microenvironment. The ultrathin nanosheets can generate O2 through the water splitting reaction and produce massive reactive oxygen species (ROS) under near infrared light irradiation. Meanwhile, the unique photothermal property of the conjugated polymer nanosheets generates hyperthermia under irradiation. Consequently, they are able to maximize the immunogenic cell death (ICD) performance by inducing adequate damage‐related molecular patterns in hypoxic tumors. Other than fostering T cell infiltration by the elicited ICD, the loaded indoleamine 2,3‐dioxygenase in nanosheets can reverse the immunosuppression and empower ICD effect for efficient T cells priming. In vivo experiments conclusively prove that the designed polymer nanosheets exhibit great potential for tumor eradication, metastasis prevention, as well as long‐term survival. Such a photocatalytic platform opens up new paths for reversing immunosuppression in immune‐cold tumors and broadens the application of polymer‐based nanosheets for cancer therapy.

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“…demonstrated that through the induction of mitophagy and apoptosis, icaritin can motivate and promote ICD within both mouse and human HCC cells ( Figure ). [ 121 ] Just given a low dose of icaritin and doxorubicin, the synergistic NPs rebuilt immunosuppressive microenvironment and caused strong immune memory in the body. Icaritin induces both apoptosis and mitophagy and subsequently activates ICD relative biomarkers in HCC tumor cells.…”

Section: Therapeutic Advances For Hcc Managementmentioning

confidence: 99%

Nanotechnology for Hepatocellular Carcinoma: From Surveillance, Diagnosis to Management

Wang

Liang

et al. 2021

Small

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Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer‐related death worldwide. However, the clinical diagnosis and treatment modalities are still relatively limited, which urgently require the development of new effective technologies. Recently, nanotechnology has gained extensive attention in HCC surveillance, imaging and pathological diagnosis, and therapeutic strategies. Typically, nanomedicines have been focused on early HCC diagnosis and precise treatment of advanced HCC, which has developed and improved a variety of new technologies and agents for future clinical practice. Furthermore, strategies of facilitating drug release and delivery in current treatment processes such as ablation, systematic therapy, transcatheter arterial chemoembolization, molecular targeted therapy, and immune‐modulating therapy have also been studied widely. This review summarizes the recent advances in this area according to current clinical HCC guidelines: 1) Nanoparticle‑based HCC surveillance; 2) Nanotechnology for HCC diagnosis; 3) Therapeutic advances for HCC Management; 4) Limitations of applications in nanotechnology for HCC; 5) Conclusions and perspectives. Although there are still many limitations and difficulties to overcome, the investigations of nanomedicines are believed to show potential applications in clinical practice.

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Icaritin Exacerbates Mitophagy and Synergizes with Doxorubicin to Induce Immunogenic Cell Death in Hepatocellular Carcinoma

Cited by 262 publications

References 40 publications

Mitophagy Receptors in Tumor Biology

Mitophagy Receptors in Tumor Biology

Reversing Immunosuppression in Hypoxic and Immune‐Cold Tumors with Ultrathin Oxygen Self‐Supplementing Polymer Nanosheets under Near Infrared Light Irradiation

Nanotechnology for Hepatocellular Carcinoma: From Surveillance, Diagnosis to Management

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