International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2021.300.307IbrahimTarek S. TaherEhab S. AltyarAhmed E. Y. RizgWaleed 52021175Background and Objective: Thyroid hormones play an important role in normal development, growth and metabolism. Thyroid hormones have been linked to the pathophysiology of different cancer types for over a century, the aim of this work is to potentiation the anticancer activity of L-thyroxine (LT) by conjugating with Trans-Activator of Transcription (TAT) peptide against cervical cancer. Materials and Methods: To enhance the anticancer activity of L-thyroxine (LT) for ovarian cancer cells, LT was conjugated with TAT then characterized for size, Zeta potential and PDI. Biological evaluation as cytotoxicity, cell cycle analysis, annexin-V and caspase-3 were evaluated. Results: The prepared formula was conjugated with HIV-TAT peptide, the prepared formula observed to be in nanometer scale and low PDI size (0.232) with 140.3 nm size. There was a 2.3-fold increase in apoptosis and a 4.3-fold increase in necrosis of the HeLa cells when incubated with the LT-TAT formula when compared to control cells. This increased apoptosis was also associated with increased caspase-3 in treated cells compared to the raw-LT group. Evaluation of cell cycle data showed a substantial arrest of the G2-M phase of the HeLa cells when incubated with LT-TAT NPs. At the same time, a dramatically increased number of pre-G1 cells showed the full apoptotic potential of the LT when administered via the proposed formulation. statistical analysis used in the study was the one-way analysis of variance (ANOVA), followed by the Tukey test. Conclusion: The upregulation of caspase-3 established the superiority of the LT-TAT approach to ovarian cancer. 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