Epinephrine Stimulates Cell Proliferation and Induces Chemoresistance in Myeloma Cells through the β-Adrenoreceptor in vitro

Abstract

Objectives: To explore the effect of the β-adrenoreceptor signaling pathway on myeloma cells. Methods: The myeloma U266 cell line was treated with epinephrine and propranolol. Cell proliferation was analyzed by MTS assay. Apoptosis was detected by flow cytometry. The β-receptor subtype and the key enzyme of epinephrine were identified by reverse transcription polymerase chain reaction (RT-PCR). Results: Epinephrine (5-50 μ<smlcap>M</smlcap>) promoted U266 cell growth in a dose-dependent manner and neutralized the inhibition effect of bortezomib (25 and 50 ng/mL) in vitro. Cell proliferation was inhibited by a β-receptor antagonist, propranolol, at a concentration of 50-200 μ<smlcap>M</smlcap>. The proportions of early and late apoptotic cells were enhanced after treatment with propranolol. The expression of caspase 3/7, 8, and 9 was elevated in propranolol-treated myeloma cells. Both β₁- and β₂-adrenoceptor mRNAs were expressed in the U266 cell line. Key enzymes dopamine hydroxylase and tyrosinehydroxylase were identified in myeloma cells. Conclusions: Our results reveal that epinephrine stimulates myeloma cell growth in vitro while the β-blocker propranolol has an antiproliferative effect, indicating that stress hormones may trigger the progression of myeloma.

β‐Adrenoceptor regulates contraction and inflammatory cytokine expression of human bladder smooth muscle cells via autophagy under pathological hydrostatic pressure

“…The activation of autophagy attenuated the expression of MCP‐1, IL‐6, and RANTES in hBSMCs induced by HP for 6 h, whereas the inhibition of autophagy aggravated the increasing trends. Moreover, consistent with a previous study showing that ATG4B overexpression decreases the expression of contractile proteins in vascular smooth muscle cells through the upregulation of autophagy, 24 our results indicate that autophagy negatively regulates the contraction of pressured hBSMCs. These conflicting findings are possibly due to cell‐specific autophagy and condition‐specific autophagy.…”

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

“…β-adrenergic signaling induced by chronic stress in cancer cells, β2-adrenergic signaling promotes proliferation and survival 230,231 Pancreatic ductal adenocarcinoma, acute lymphoblastic leukemia, hepatocarcinoma.…”

“…Adrenaline stimulates myeloma cell proliferation by activating β1and β2-adrenoceptors, as indicated by the anti-proliferative effect of propranolol, a β-blocker. 230 In a model of chemically induced hepatocarcinogenesis, adrenaline promotes cancer cell proliferation and survival triggered by β2-adrenergic signaling. It also inhibits autophagy and promotes HIF-1α stabilization stimulating gene expression of angiogenic factors.…”

Construction of differential expression plasmids of NGF to detect its influence on PC12 cell neuronal differentiation

“…Numerous studies have reported that cancer angiogenesis and lymphangiogenesis occur in the cancer microenvironment (29)(30)(31)(32), but the potential biological effects of cancer-related neurogenesis have been rarely reported. Tumor cells can use a large number of factors secreted by nerve fibers to create microenvironments to help them survive and proliferate, such as epinephrine, catecholamines and adrenaline (7,(33)(34)(35)(36)(37)(38). At the same time, tumor cells can stimulate the production of neurons by secreting neurotrophic factors and axonal guiding molecules (11).…”