Exploring the potential pro-apoptotic, antiproliferative and antimetastatic activities of natural products

The molecular complexity of cancers and therapy-related side effects often limit efficacy of numerous anti-tumor therapies, and warrant development of new drugs with preferential cytotoxic activity against cancer cells. Natural products are considered as promising tools for the treatment of cancer. I have had a long-standing interest in developing potent and safe anticancer drugs. One of the compounds that we pursued was thymoquinone (TQ), the most bioactive constituent of black seed oil. We found out that TQ suppresses human hepatocellular carcinoma (HCC) and medulloblastoma (MB) cell growth and metastasis via induction of apoptosis and inhibition of oxidative stress, downregulation of IL-8 and NF-κB expression and upregulation of expression of NF-κB negative regulators A20-binding inhibitor of NF-κB activation- (ABIN-) 1 and 2. Further, we recently examined cytotoxic potencies of extracts of Willow leaves Salix safsaf and found out that they exhibited selective cytotoxicity against four cancer cell lines (HCT-116 colorectal adenocarcinoma, MCF-7 mammary adenocarcinoma and HepG2 hepatocellular carcinoma cells), but not toward noncancerous skin fibroblast (BJ-1) and breast fibroblast (MCF-12) cells. The observed cytotoxicity was mediated by apoptosis via reactive oxygen species (ROS)-independent mechanism. Further, treatment with Salix safsaf extract upregulated pro-apoptotic protein and mRNA of caspase-3, p53 and Bax, and downregulated protein and mRNA of the anti-apoptotic marker Bcl-2. This preferential pro-apoptotic activity warrants investigation of the active principles in willow leaves in pre-clinical and clinical cancer trials. Moreover, we found promising antitumor compounds in the plant Premna resinosa and the Red Sea sponges Xestospongia testudinaria and Haliclona sp