Accumulating evidence has shown a vital role of stress-regulatory hormones, including epinephrine, in the progression of numerous cancers, including T cell lymphoma. Further, the antitumor and chemosensitizing potential of propranolol, an inexpensive β-adrenergic receptor antagonist has also been reported against breast, colon, ovarian, and pancreatic cancers. However, in vivo antitumor and chemopotentiating activity of propranolol have not yet been examined against malignancies of hematological origin, including T cell lymphoma. Therefore, the present study is designed to evaluate the antitumor and chemopotentiating action of propranolol in a T cell lymphoma murine model. In this study, T cell lymphoma-bearing mice were treated with vehicle alone (PBS) or containing propranolol followed by administration of with or without cisplatin. The progression of the tumor was assessed along with analysis of tumor cell apoptosis, glucose metabolism, pH regulation, and antitumor immune response. The apoptosis was estimated by cellular and nuclear morphology analysis through Wright-Giemsa, annexin-V, and DAPI staining. ELISA was used to detect the epinephrine level in serum. The glucose, lactate, and NO levels were measured in the tumor ascitic fluid by calorimetric methods. RT-PCR and Western blot were used to assess the levels of various crucial regulators at gene and protein levels, respectively. Our results showed that propranolol exerts antitumor as well as chemopotentiating ability in DL-bearing mice by altering apoptosis, glycolysis, acidification of TME, and immunosuppression.
Keywords: Apoptosis; Chemosensitization; Glycolysis; Immunoactivation; T cell Lymphoma; Tumor acidosis.
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