Coompo Research Chemicals

Psoralidin possessing anticancer and chemopreventive properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells with no toxicity toward normal tissues. Endogenous TRAIL plays an important role in immune surveillance and defence against cancer cells. Coumarins can modulate TRAIL-mediated apoptosis in cancer cells. We examined the cytotoxic and apoptotic activities of psoralidin in combination with TRAIL on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining and mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression was analyzed using flow cytometry. Psoralidin enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and depolarization of mitochondrial membrane potential. Our study indicated that psoralidin augmented the anticancer effects of TRAIL and confirmed a potential use of coumarins in cancer chemoprevention.

The protein kinase Akt plays an important role in cell proliferation and survival in many cancers, including prostate cancer. Due to its kinase activity, it serves as a molecular conduit for inhibiting apoptosis and promoting angiogenesis in most cell types. In most of the prostate tumors, Akt signaling is constitutively activated due to the deletion or mutation of the tumor suppressor PTEN, which negatively regulates phosphatidylinositol 3-kinase through lipid phosphatase activity. Psoralidin inhibits Akt phosphorylation, and its consequent activation in androgen-independent prostate cancer (AIPC) cells. Furthermore, ectopic expression of Akt renders AIPC cells resistant to chemotherapy; however, psoralidin overcomes Akt-mediated resistance and induces apoptosis in AIPC cells. While dissecting the molecular events, both upstream and downstream of Akt, we found that psoralidin inhibits phosphatidylinositol 3-kinase activation and transcriptionally represses the activation of nuclear factor-kappaB and its target genes (Bcl-2, Survivin, and Bcl-xL, etc.), which results in the inhibition of cell viability and induction of apoptosis in PC-3 and DU-145 cells. Interestingly, psoralidin selectively targets cancer cells without causing any toxicity to normal prostate epithelial cells. In vivo xenograft assays substantiate these in vitro findings and show that psoralidin inhibits prostate tumor growth in nude mice. Our findings are of therapeutic significance in the management of prostate cancer patients with advanced or metastatic disease, as they provide new directions for the development of a phytochemical-based platform for prevention and treatment strategies for AIPC.
Psoralidin inhibits forskolin-induced corticotrophin releasing factor gene transcription. Recently, it has shown activity in vitro against gastric, colon, prostate, and breast cancer lines.

Psoralidin has shown positive results in the forced swim test. Psoralidin raised 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the brain. Dopamine levels changed as well as a result of psoralidin consumption. Stress hormones in mice such as serum corticotropin releasing factor, adrenal corticotropin releasing hormone, and corticosterone were reduced after psoralidin administration.