Celastrol attenuates the inflammatory response by inhibiting IL‑1β expression in triple‑negative breast cancer cells

Abstract

IL‑1 promotes cancer cell proliferation and invasiveness in various malignancies, such as breast and colorectal cancer. In the present study, the functional roles of IL‑1β (IL1B) and the inhibitory effect of celastrol on IL1B expression were investigated in triple‑negative breast cancer (TNBC) cells. The data revealed that celastrol markedly decreased IL1B expression and suppressed TNBC cell proliferation in a dose‑dependent manner. The levels of IL1B and IL8 mRNA were significantly increased in TNBC cells compared with non‑TNBC cells. In addition, IL1B augmented the expression levels of IL8 as well as matrix metalloproteinases (MMPs), including MMP‑1 and MMP‑9, in TNBC cells. Furthermore, IL1B expression was decreased by a specific MEK1/2 inhibitor, MEK162. Celastrol also promoted IL1B downregulation through the suppression of the MEK/ERK‑dependent pathway. Furthermore, the results also revealed a decrease in IL1B‑induced IL8, MMP‑1, and MMP‑9 expression in response to celastrol treatment. The induction of cellular invasion by IL1B was also markedly decreased by celastrol. Collectively, the present study results suggested celastrol as an effective drug for the treatment of TNBC, involving a reduction in IL1B expression, activity or signaling pathways.

Keywords: celastrol; interleukin 1β; interleukin 8; matrix metalloproteinase 1; matrix metalloproteinase 9; triple‑negative breast cancer.