Hepatocellular carcinoma is one of the most common malignant tumors worldwide. For the difficulty of the giving sufficient dose because of the poor liver function and the low sensitivity of hepatoma cells for the chemotherapeutic agents, chemotherapy adds little to overall survival of hepatocellular carcinoma patients. The induction of terminal differentiation in tumor cells represents a possible therapeutic strategy with less toxicity. Gekko sulfated polysaccharides, isoverbascoside, Ginsenoside-Rh2, Camptothecin, 9-nitro-camptothecin, tachyplesin, Matrine, tylophorine, 7-OH-4-CH(3)-coumarin and arsenic trioxide are known to have a differentiation-inducing capability on hepatocellular carcinoma in vitro and/or in vivo. Although the therapeutic effect of the differentiation-inducing agents may not be potent when compared with that of conventional chemotherapeutic agents, they have multiple therapeutic targets, low toxicity and less probability of drug resistance. More data are required on the molecular mechanisms of therapeutic effects, dose response and potential toxicities.
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