Synergistic efficacy of telomerase-specific oncolytic adenoviral therapy and histone deacetylase inhibition in human hepatocellular carcinoma

Lin, Zhong‐Zhe; Hu, Mickey C.T.; Hsu, Chiun; Wu, Yao‐Ming; Lu, Yen‐Shen; Ho, Ja‐an Annie; Yeh, Shiou–Hwei; Chen, Pei‐Jer; Cheng, Ann‐Lii

doi:10.1016/j.canlet.2023.216063

Cited by 4 publications

(2 citation statements)

References 41 publications

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“…For example, Lin et al demonstrated a synergistic therapeutic effect of pan-HDACi AR42 and telomerase-specific oncolytic adenovirus therapy. AR42 significantly enhanced telomerase-induced apoptosis in HCC tumor cells (122). These studies all showed the strong potential of HDACis in the field of HCC therapy.…”

Section: Hdac Inhibitors For Hcc Treatmentmentioning

confidence: 54%

HDAC inhibitors enhance the anti-tumor effect of immunotherapies in hepatocellular carcinoma

Shen

Duan

et al. 2023

Front. Immunol.

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Hepatocellular carcinoma (HCC), the most common liver malignancy with a poor prognosis and increasing incidence, remains a serious health problem worldwide. Immunotherapy has been described as one of the ideal ways to treat HCC and is transforming patient management. However, the occurrence of immunotherapy resistance still prevents some patients from benefiting from current immunotherapies. Recent studies have shown that histone deacetylase inhibitors (HDACis) can enhance the efficacy of immunotherapy in a variety of tumors, including HCC. In this review, we present current knowledge and recent advances in immunotherapy-based and HDACi-based therapies for HCC. We highlight the fundamental dynamics of synergies between immunotherapies and HDACis, further detailing current efforts to translate this knowledge into clinical benefits. In addition, we explored the possibility of nano-based drug delivery system (NDDS) as a novel strategy to enhance HCC treatment.

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Section: Hdac Inhibitors For Hcc Treatmentmentioning

confidence: 54%

HDAC inhibitors enhance the anti-tumor effect of immunotherapies in hepatocellular carcinoma

Shen

Duan

et al. 2023

Front. Immunol.

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“…The integration of oncolytic and epigenetic therapies is a promising strategy for the management of multiple cancers [ 203 ]. Telomelysin, a telomerase-specific oncolytic adenovirus, and AR42, an HDACi, have shown anti-cancer properties in pre-clinical studies involving human HCC [ 204 ].…”

Section: Therapeutic Potential Of Targeted Epigenetic Modifiers and M...mentioning

confidence: 99%

Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

Li,

Wang,

Zhao

et al. 2024

Metabolites

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Epigenetic and metabolic reprogramming alterations are two important features of tumors, and their reversible, spatial, and temporal regulation is a distinctive hallmark of carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, is a new entry point for tumor therapy. Moreover, metabolic reprogramming drives hepatocellular carcinoma (HCC) initiation and progression, highlighting the significance of metabolism in this disease. Exploring the inter-regulatory relationship between tumor metabolic reprogramming and epigenetic modification has become one of the hot directions in current tumor metabolism research. As viral etiologies have given way to metabolic dysfunction-associated steatotic liver disease (MASLD)-induced HCC, it is urgent that complex molecular pathways linking them and hepatocarcinogenesis be explored. However, how aberrant crosstalk between epigenetic modifications and metabolic reprogramming affects MASLD-induced HCC lacks comprehensive understanding. A better understanding of their linkages is necessary and urgent to improve HCC treatment strategies. For this reason, this review examines the interwoven landscape of molecular carcinogenesis in the context of MASLD-induced HCC, focusing on mechanisms regulating aberrant epigenetic alterations and metabolic reprogramming in the development of MASLD-induced HCC and interactions between them while also updating the current advances in metabolism and epigenetic modification-based therapeutic drugs in HCC.

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Study on antihepatocellular carcinoma effect of 6-shogaol and curcumin through network- based pharmacological and cellular assay

Jin,

Jiao,

Lian

et al. 2023

Preprint

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Background Hepatocellular carcinoma currently has the third highest mortality rate in the world. Patients with hepatocellular carcinoma are on the rise and at a younger age, but research into the pharmacological effects of cancer is mostly single-component, and natural plant products can have additive or synergistic effects that can better amplify the effects of intervention in cancer. Aim To evaluate the synergistic therapeutic effects of 6-shogaol and curcumin against hepatocellular carcinoma line HepG2 cells. Methods In this study, a network pharmacology approach was used to predict and validate the mol ecular targets and pathways of the hepatocellular carcinoma (HCC) of 6-shogaol and curcumin in combination and to investigate their mechanism of action. The results were also validated by cellular assays.HepG2 cells were treated with 6-shogaol and curcumin as well as the combination of the two. The combination index (CI) of 6-shogaol and curcumin in HepG2 cells was calculated using Compusyn software according to the Chou-Talalay equation.The synergistic anti-cancer effect was next investigated by MTT assay, apoptosis assay and cell cycle assay. The combined anti-hepatocellular carcinoma effect of the Ras-mediated PI3K/AKT and MAPK signalling pathways was analysed using protein blotting assays. Results A network pharmacology-based screening identified 72 core targets of 6-curcumin and curcumin in hepatocellular carcinoma, and predicted that the main signalling pathway is the Ras signalling pathway. The anti-cancer effects of 6-shogaol and curcumin were validated in cell-based assays and the optimal synergistic concentrations of 5 µmoL/L for 6-shogaol and 30 µmoL/L for curcumin were determined. 6-shogaol and curcumin synergistically blocked the cell cycle in the G2/M phase and promoted apoptosis. Immunoblot analysis confirmed for the first time the combined action of both in down-regulating the Ras-mediated PI3K/AKT and MAPK signaling pathways. In addition, 6-shogaol and curcumin acting together down-regulated Cyclin-B, CDK-1, Bcl-2, and up-regulated BAX. Conclusion 6-shogaol and curcumin act synergistically to alter the morphology of hepatocellular carcinoma cells, block the cell cycle in the G2/M phase, inhibit proliferation and division, and effectively promote late apoptosis. The combined action of these two components provides a theoretical basis for the further development of novel anti-liver cancer products.

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Synergistic efficacy of telomerase-specific oncolytic adenoviral therapy and histone deacetylase inhibition in human hepatocellular carcinoma

Cited by 4 publications

References 41 publications

HDAC inhibitors enhance the anti-tumor effect of immunotherapies in hepatocellular carcinoma

HDAC inhibitors enhance the anti-tumor effect of immunotherapies in hepatocellular carcinoma

Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

Study on antihepatocellular carcinoma effect of 6-shogaol and curcumin through network- based pharmacological and cellular assay

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