Nanoencapsulation of B-toxin from herbal extracts: Targeting HTLV-1 protease and ATLL

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 1 protease (HTLV-1 PR). HTLV-1 protease (HTLV-1 PR) is an aspartic acid protease and a promising therapeutic target for human immunodeficiency virus (HIV) PR inhibitors.

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-1-infected-MT2, 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 gamma1 (HTLV-1 PR: hFc gamma1) against HTLV-1.

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-1-infected-MT2 cell line, in the absence of recombinant peptide, was (38.98 ± 0.23) and in the presence was (16.18 ± 2.03) in 72 hr (P<0.001). This indicates a double inhibitory effect in the presence of the peptide. The enzymatic effect of HTLV-1-protease on its fluorochrome substrate in the presence of TB and isoTB showed nearly complete enzyme inhibition.

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.