Triptolide: Novel Anticancer Agent for Chemoresistant Cancer Cells that are Caspase-3 Deficient

Cancer is a major cause of death worldwide and there are over 100 different types of cancers. The current treatment strategies for cancer patients such as surgery, chemotherapy and radiation or the combination of radiotherapy and chemotherapy may have successfully increased five-year survival rates. However, the long-term survival rates remain poor due to cancer relapse, tumor resistance and metastasis. Treatments such as chemotherapy and radiation are known to have untoward side effects on normal cells. Therefore, it is imperative to develop safer and noninvasive treatments. The use of natural products in the fight against cancer is one possible way of slowing tumor growth and may allow us to design more effective therapies. In this review, we examine the central role played by the key apoptotic executioner protease, caspase-3 and propose molecular mechanisms by which cancer cells can evade anticancer treatments by mutating this protein. Triptolide, a Chinese herb, has been used for over 200 years to treat anti-inflammatory and autoimmune disorders. A considerable body of data indicates that triptolide has potent anticancer properties. We provide supporting evidence demonstrating that caspase-3 independent cell, lysosomalmediated death pathways induced by triptolide, a Chinese herb, may provide effective novel antitumor treatment modalities.