Mulberry leaf extract inhibit hepatocellular carcinoma cell proliferation via depressing IL-6 and TNF-α derived from adipocyte

Epidemiological studies have revealed that obesity and being overweight are associated with increased cancer risk. Adipose tissue is regarded as an endocrine organ that secretes proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which are related to the progression of hepatocellular carcinoma (HCC). In this study, adipocytes from 3T3-L1 cells were induced and stained with Oil Red O, which revealed marked intracellular lipid accumulation. Adding 15% conditioned medium (CM) from adipogenic-differentiated 3T3-L1 cells, which contained adipocyte-derived factors, to a culture medium of HepG2 cells was discovered to promote cell proliferation by a factor of up to 1.3 compared with the control. Mulberry leaf extract (MLE), with major components including chlorogenic acid and neochlorogenic acid, was revealed to inhibit CM-promoted HepG2 cell proliferation. The inhibitory effect of MLE on the proliferation of the signal network was evaluated. Expression of the CM-activated IκB/NFκB, STAT3, and Akt/mTOR pathways were reduced when MLE was administered. Although adipocyte-derived factors are complex, administrating anti-TNF-α and anti-IL-6 revealed that MLE blocks signal activation promoted by TNF-α and IL-6. Taken together, these results demonstrated that MLE targets the proliferation signal pathway of the inflammatory response of adipocytes in HCC and could be to prevent obesity-mediated liver cancer.