Advances on Delivery of Cytotoxic Enzymes as Anticancer Agents

Asrorov, Akmal M.; Muhitdinov, Bahtiyor; Tu, Bin; Mirzaakhmedov, Sharafitdin; Wang, Huiyuan; Huang, Yongzhuo

doi:10.3390/molecules27123836

Cited by 7 publications

(2 citation statements)

References 195 publications

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“…However, in the present study, TCS barely promoted the autophagic death of HCC cells. Recently, Hu et al detected by proteomics that TCS inhibited nuclear proliferation factors in human choriocarcinoma cell lines, mainly inducing caspase-mediated apoptosis in cancer cells [ 41 ]. Caspase 8 is a key protease in apoptosis caused by exogenous factors [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular Carcinoma

Wang

Zhang

et al. 2023

IJMS

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Trichosanthin (TCS) is a type I ribosome-inactivating protein extracted from the tuberous root of the plant Trichosanthes. TCS shows promising potential in clinical drug abortion, anti-tumor and immunological regulation. However, the molecular mechanisms of its anti-tumor and immune regulation properties are still not well discovered. In the present study, we investigated the anti-tumor activity of TCS in hepatocellular carcinoma (HCC), both in vitro and in vivo. Both HCC cell lines and xenograft tumor tissues showed considerable growth inhibition after they were treated with TCS. TCS provoked caspase-mediated apoptosis in HCC cells and xenograft tumor tissues. The recruitment of CD8+ T cells to HCC tissues and the expression of chemokines, CCL2 and CCL22, were promoted upon TCS treatment. In addition, TCS induced an upregulation of Granzyme B (GrzB), TNF-α and IFN-γ in HCC tissues, which are the major cytotoxic mediators produced by T cells. Furthermore, TCS also resulted in an increase of mannose-6-phosphate receptor (M6PR), the major receptor of GrzB, in HCC tissues. In summary, these results suggest that TCS perhaps increases T-cell immunity via promoting the secretion of chemokines and accelerating the entry of GrzB to HCC cells, which highlights the potential role of TCS in anti-tumor immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Trichosanthin Promotes Anti-Tumor Immunity through Mediating Chemokines and Granzyme B Secretion in Hepatocellular Carcinoma

Wang

Zhang

et al. 2023

IJMS

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“…Ultrasound‐, light‐, near‐IR‐ and other physical stimuli‐responsive systems have attracted more attention recently. A combination of multiple strategies is used to improve the efficiency of CPP‐based DDS (Asrorov, 2022; Zhang & Cui, 2018). In Scheme 2, strategies that activate CPP‐based DDS are overviewed.…”

Section: Strategies To Enhance the Efficiency Of Cppsmentioning

confidence: 99%

Cell penetrating peptides: Highlighting points in cancer therapy

Asrorov

Wang

Zhang

et al. 2023

Drug Development Research

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Cell‐penetrating peptides (CPPs), first identified in HIV a few decades ago, deserved great attention in the last two decades; especially to support the penetration of anticancer drug means. In the drug delivery discipline, they have been involved in various approaches from mixing with hydrophobic drugs to the use of genetically conjugated proteins. The early classification as cationic and amphipathic CPPs has been extended to a few more classes such as hydrophobic and cyclic CPPs so far. Developing potential sequences utilized almost all methods of modern science: choosing high‐efficiency peptides from natural protein sequences, sequence‐based comparison, amino acid substitution, obtaining chemical and/or genetic conjugations, in silico approaches, in vitro analysis, animal experiments, etc. The bottleneck effect in this discipline reveals the complications that modern science faces in drug delivery research. Most CPP‐based drug delivery systems (DDSs) efficiently inhibited tumor volume and weight in mice, but only in rare cases reduced their levels and continued further processes. The integration of chemical synthesis into the development of CPPs made a significant contribution and even reached the clinical stage as a diagnostic tool. But constrained efforts still face serious problems in overcoming biobarriers to reach further achievements. In this work, we reviewed the roles of CPPs in anticancer drug delivery, focusing on their amino acid composition and sequences. As the most suitable point, we relied on significant changes in tumor volume in mice resulting from CPPs. We provide a review of individual CPPs and/or their derivatives in a separate subsection.

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