Nanoencapsulation of B-toxin from herbal extracts: Targeting HTLV-۱ protease and ATLL

Objective(s): Toxin B and isotoxin B (TB, isoTB) are major constituents of the Taxus baccata tree. This study investigates the inhibitory effect of TB and isoTB on adult T-cell leukemia/lymphoma (ATLL), particularly on human T-lymphotropic virus type ۱ protease (HTLV-۱ PR). HTLV-۱ protease (HTLV-۱ PR) is an aspartic acid protease and a promising therapeutic target for human immunodeficiency virus (HIV) PR inhibitors. Materials and Methods: The anticancer properties of T. baccata plant components encapsulated in PLGA nanoparticles (NPs/ PLGA/TB) were evaluated by in vitro assays using different cell lines. Cancerous cell lines, including HTLV-۱-infected-MT۲, were treated with varying concentrations of TB and alcoholic extract, and a combined peptide was designed and expressed using recombined NPs/PLGA/TB in a human Fc gamma۱ (HTLV-۱ PR: hFc gamma۱) against HTLV-۱. Results: Our results show that the viability of cancer cells after NPs/ PLGA/TB treatment significantly decreased in a time- and dose-dependent manner using the MTT assay. The inhibitory effect of NPs/ PLGA/TB on the HTLV-۱-infected-MT۲ cell line, in the absence of recombinant peptide, was (۳۸.۹۸ ± ۰.۲۳) and in the presence was (۱۶.۱۸ ± ۲.۰۳) in ۷۲ hr (P<۰.۰۰۱). This indicates a double inhibitory effect in the presence of the peptide. The enzymatic effect of HTLV-۱-protease on its fluorochrome substrate in the presence of TB and isoTB showed nearly complete enzyme inhibition. Conclusion: These findings present a promising avenue for introducing therapeutic agents with anticancer properties to treat progressive cancers, such as viral ATLL, and inducing effective antiviral responses.

کلیدواژه ها:

Cancer ، Human T-cell leukemia - virus type ۱ (HTLV-۱) ، Nanoparticles ، Paclitaxel ، Poly lactic-co-glycolic acid - (PLGA) ، Retrovirus