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World J Gastroenterol. Apr 14, 2007; 13(14): 2037-2043
Published online Apr 14, 2007. doi: 10.3748/wjg.v13.i14.2037
Multifactorial nature of hepatocellular carcinoma drug resistance: Could plant polyphenols be helpful?
Natale D’Alessandro, Paola Poma, Giuseppe Montalto
Natale D’Alessandro, Paola Poma, Department of Pharma-cological Sciences, University of Palermo, Italy
Giuseppe Montalto, Department of Clinical Medicine, University of Palermo, Palermo, Italy
Author contributions: All authors contributed equally to the work.
Supported by PRIN MIUR 2005051211 2005
Correspondence to: Natale D’Alessandro, Department of Pharmacological Sciences, University of Palermo, Via del Vespro 129, Palermo 90127, Italy. dalessan@unipa.it
Telephone: +39-91-6553258 Fax: +39-91-6553249
Received: October 7, 2006
Revised: December 1, 2006
Accepted: December 8, 2006
Published online: April 14, 2007
Abstract

Primary hepatocellular carcinoma (HCC) is a quite frequent tumor which results in high mortality and most often exhibits a poor response to present drug therapies. Clearly, a thorough understanding of the biological bases of this malignancy might suggest new strategies for its treatment. Here we examine the evidences that both “pharmacological” mechanisms (e.g. drug transporter or detoxification enzyme over-expression) and alterations in other critical factors, including the IAPs (Inhibitory of Apoptosis Proteins), involved in enhancement of cell survival and proliferation may determine the therapeutic resistance of HCC; we also underline the possible role in the process of the activation of transcription factors, like NF-κB, capable of contemporaneously up-regulating the mechanisms discussed. On this basis, we finally comment on the possible use of natural multi-targeted antitumoral agents like plant polyphenols to achieve sensitization to treatments in HCC.

Keywords: Hepatocellular carcinoma; Drug resistance; Drug transporters; Inhibition of cell death; IAPs; NF-κB; Plant polyphenols