Plant Derived Inhibitor Sulforaphane in Combinatorial Therapy Against Therapeutically Challenging Pancreatic Cancer

Abstract

Pancreatic cancer is one of the most aggressive human cancers and is expected to surpass breast cancer to become the third chief cause of cancer-related deaths in the United States. While conventional treatment approaches such as surgery and classic chemotherapy have slightly improved the relative five year survival rate to 8% yet it is the lowest survival rate for any major cancer. This emphasizes the serious need of more effective and well tolerated therapies to reverse the poor prognosis of the defined neoplasm. Aberrant expression of histone deacetylase (HDAC) enzymes has been implicated in pancreatic cancer signalling. The inhibitors of these enzymes namely HDAC inhibitors (HDACi) are the novel agents which are currently being tested. These inhibitors modulate both histone and nonhistone proteins and have shown multiple biological effects including cell cycle arrest, differentiation and apoptosis in several cancer models. This article focuses on plant-derived HDAC inhibitor Sulforaphane (SFN) as a promising antipancreatic cancer agent. Moreover, we discuss the distinct molecular mechanisms triggered by SFN to exert cytotoxic effect in the predefined cancer models. Finally we describe the combinatorial therapeutic strategy involving SFN with other anticancer agents. This novel approach circumvents herculean cancer chemoresistance and alleviates toxicity, the main drawbacks of monotherapy.