Title:Plant Derived Inhibitor Sulforaphane in Combinatorial Therapy Against Therapeutically Challenging Pancreatic Cancer
Volume: 17
Issue: 3
Author(s): Shabir Ahmad Ganai, Romana Rashid, Ehsaan Abdullah and Mohammad Altaf
Affiliation:
Keywords:
Sulforaphane, pancreatic cancer, combinatorial therapy, HDACs, HDACi.
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.
