Effects of Lycopene and Sho-saiko-to on Hepatocarcinogenesis in a Rat Model of Spontaneous Liver Cancer

Abstract

The Long-Evans Cinnamon (LEC) rat is a well-characterized model of spontaneous hepatocarcinogenesis. It has been shown that dietary administration of lycopene or the herbal medicine Sho-saiko-to (TJ-9) has anticarcinogenic activity, although the mechanism by which these products protect against carcinogenesis is not well known. We investigated the outcome of administration of lycopene and TJ-9 on the occurrence of hepatic neoplasia in LEC rats. A diet containing 0.005% lycopene (originally the product of tomato oleoresin containing 13% lycopene) and 1% TJ-9 (crude extracts of 7 herbs: bupleurum root, pinellia tuber, scutellaria root, jujube fruit, ginseng root, glycyrrhiza root, and ginger rhizome) was administered from 6 weeks of age until the rats were sacrificed at 76 weeks of age, at which time most of the nontreated animals were known to have hepatocellular carcinoma (HCC). Development of HCC in treated groups was analyzed histologically by comparison with untreated controls. Glutathione S-transferase placental form (GST-P) was analyzed by an immunohistochemical method. Concentration of copper, iron, and zinc, which appear to play a role in hepatocarcinogenesis in LEC rats, was analyzed. The percent areas of HCC in the liver specimens of control, lycopene, and TJ-9 groups were 17.9 +/- 17.1%, 27.2 +/- 20.8%, and 27.6 +/- 18.4%, respectively. These intergroup differences were not significant. The percent area, number of areas, and mean size of area staining positively for GST-P revealed no significant differences between the groups. The number of GST-P-positive areas within the HCC lesions was greater in the TJ-9 group than in the control or lycopene group (p = 0.024 and p = 0.012, respectively). The study also demonstrated a lower concentration of iron in livers of the lycopene group than the control group (p = 0.019). There were no differences in serum alpha-fetoprotein levels or the cumulative survival rates between the groups. In conclusion, long-term administration of lycopene or TJ-9 did not reduce the risk of hepatocarcinogenesis in LEC rats.

Multitargeted therapy of cancer by lycopene

“…In addition, no reduction in tumors of colon, kidney or liver was observed. This lack of efficacy toward the prevention of liver cancer is consistent with the results of Watanabe et al [57] who reported that dietary lycopene did not prevent liver cancer in Long-Evans Cinnamon rats, a model of spontaneous hepatocarcinogenesis.…”

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

“…Studies conducted by Gradelet et al [172,173] showed that dietary lycopene treatment failed to show any modifying effects, either on the initiation or on the promotional phases of hepatocarcinogenesis induced by AFB1 in male Wistar rats. Similar results were reported by Watanabe et al [183] indicating that lycopene failed to produce any chemopreventive effect against spontaneous HCC in Long-Evans Cinnamon rats. Few other studies conducted with different treatment regimens of lycopene arrived at conclusions that were contrary to the aforementioned studies.…”

C5 Extract Induces Apoptosis in B16F10 Murine Melanoma Cells through Extrinsic and Intrinsic Apoptotic Pathways and Sub-G1 Phase Arrest

“…C5E is composed of ethanol extracts from a mixture of Ginseng, Chaga, Pinellia Tuber, Sparganium Rhizome, Alpinia Rhizome, Cinnamon Bark, Astragalus Root, Psoraleae Semen, Evodia Fruit, and Meliae Fructus. There have been several reports regarding these materials, but this study is the first to analyze the effect of these extracts on B16F10 melanoma cells [23][24][25]. In this study, the following effects of C5E ethanol extracts were examined: inhibition of the proliferation of B16F10 and keratinocyte cells, apoptotic signaling pathway in B16F10 cells, induction of cell cycle arrest in B16F10 cells, and inhibition of the proliferation of B16F10 cells when combined with vinblastine.…”