Persistent chronic stress nowadays emerges as a critical culprit contributor to the enhanced progression of many diseases, even cancer is not untouched [[1], [2], [3]]. Cancer is a multifaceted rogue and a generic term for an enormous array of disorders that can affect any part of our body irrespective of gender [4,5]. According to statistical data, cancer is the second leading cause of death; this data is frightening enough and well sufficient to generate mental turmoil among patients [4,6]. Several recent studies have shown that chronic stress harbors and provides a favorable environment obligatory for the rapid progression of cancer [1,3,7,8]. Stress leads to altered and aberrant regulation of immune cells and weakens the body's overall immune response [7,9]. Few recent reports suggest that tumor cells have the potential to generate their autocrine catecholamine loop as well as elevate stress hormone levels to reawaken the dormant cancer cells [10,11]. Among all the stress contributors, epinephrine has been regarded as one of the crucial candidates [12]. A significant increase in epinephrine levels (0.7–7.7 μg/ml) has been observed during pathophysiological conditions in contrast to normal physiological level (0–140 pg/ml) [13,14]. Epinephrine also regulates fuel metabolism during stress [15]. Available reports confirm that epinephrine elevates blood glucose and promotes glycogenolysis and gluconeogenesis [15,16].

Further, the tumor-promoting action of epinephrine is well reported in many cancers such as esophagus, breast, colon, pancreatic, gastric, ovarian, and myeloma through inducing various cancer-promoting features, including aberrant proliferation and apoptosis evasion [8,[17], [18], [19], [20], [21], [22]]. However, to date, none of the studies has examined epinephrine's cancer-promoting action in T cell lymphoma. T cell lymphoma is a malignancy of T lymphocytes, which play a crucial role in cell-mediated immunity and antitumor immunity. T cell lymphoma is considered one of the highly complex hematological malignancies in terms of its clinical management. Among all the non-Hodgkin lymphoma (NHL), T cell lymphoma alone stakes 15%, with a poor prognosis and survival, affecting a wide range of age groups [6,23].

Reprogrammed glucose metabolism is one of the most noticeable features in a wide range of cancers, including T cell lymphoma [[24], [25], [26]]. Furthermore, due to their highly proliferative nature, most cancer cells shift their glucose metabolism from oxidative phosphorylation to glycolysis to fulfill their dramatically increased biosynthetic, bioenergetic, and redox demands [5]. Though epinephrine is involved in maintaining glucose homeostasis, its role in metabolic rewiring in tumor cells has not been sufficiently unveiled. Although, in a recent study, Cui et al. reported that epinephrine induces breast cancer stem-like properties through lactate dehydrogenase A–dependent (LDHA-dependent) metabolic reprogramming [22]. However, the metabolic regulatory action of epinephrine is not yet examined in T cell lymphoma. So, to crack these conundrums, we used two different cell lines of T cell lymphoma, namely Dalton's lymphoma (DL) and human T cell lymphoma-78 (HuT-78). Dalton's lymphoma is a T cell lymphoma cell line and was established in the laboratory of Dr. Albert J. Dalton at the National Cancer Institute, Bethesda, USA [27,28]. HuT-78 is a human-origin T lymphoma cell line, derived from a white, male patient with Sezary syndrome [29].

Considering the lacunae mentioned above, the present study was designed to examine the role of epinephrine in aberrant proliferation, apoptosis, and glucose metabolism of T lymphoma cells and their underlying molecular mechanisms.