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

Epidemiological studies have revealed that obesity and being overweight are associatedwith increased cancer risk. Adipose tissue is regarded as an endocrine organ that secretesproinflammatory cytokines such as tumor necrosis factor-a (TNF-a) 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 revealedmarked intracellular lipid accumulation. Adding 15% conditioned medium (CM) from adipogenic-differentiated 3T3-L1 cells, which contained adipocyte-derived factors, to a culturemedium of HepG2 cells was discovered to promote cell proliferation by a factor of upto 1.3 compared with the control. Mulberry leaf extract (MLE), with major componentsincluding chlorogenic acid and neochlorogenic acid, was revealed to inhibit CM-promotedHepG2 cell proliferation. The inhibitory effect of MLE on the proliferation of the signalnetwork was evaluated. Expression of the CM-activated IkB/NFkB, STAT3, and Akt/mTORpathways were reduced when MLE was administered. Although adipocyte-derived factorsare complex, administrating anti-TNF-a and anti-IL-6 revealed that MLE blocks signalactivation promoted by TNF-a and IL-6. Taken together, these results demonstrated thatMLE targets the proliferation signal pathway of the inflammatory response of adipocytes inHCC and could be to prevent obesity-mediated liver cancer.