Multifactorial nature of hepatocellular carcinoma drug resistance: Could plant polyphenols be helpful?

Table 1 Major drug transporters possibly involved in the drug resistance of HCC

Transporter	Drugs interested
P-glycoprotein (MDR1, ABCB1)	Anthracyclines, Mitoxantrone, Podophyllotoxin derivatives, Taxanes, Vinca alkaloids
MRP2 (ABCC2, cMOAT)	Anthracyclines, Cisplatin, Methotrexate, Irinotecan metabolites, Vinca alkaloids
MRP3 (ABCC3)	Etoposide, Methotrexate
LRP (Major vault protein, MVP)	Cisplatin, Doxorubicin, Etoposide, 5-fluorouracil, Paclitaxel, Vincristine
TAP (Transporter associated with antigen processing)	Doxorubicin, Etoposide, Mitoxantrone, Vincristine

In normal hepatocytes, P-glycoprotein and the members of the MRP family play an important role in biliary excretory function. Also vaults have a transport function, mediating bidirectional nucleo-cytoplasmic exchange and vesicular transport of compounds, including cytostatic drugs. Physiologically, TAP translocates short peptides, mostly generated by proteasome-mediated antigenic protein degradation in the cytosol, into the lumen of the endoplasmic reticulum. All these factors may mediate chemoresistance of various malignancies: the spectrum of the drugs that they may transport does not necessarily derive from specific studies on HCC.