Dihydrotanshinone-I and Neoplasm-Metastasis

Dihydrotanshinone I (DHTS), extracted from Salvia miltiorrhiza, was found to be the most effective compound of tanshen extracts against cancer cells in our previous studies. However, the therapeutic benefits and underlying mechanisms of DHTS on ovarian cancer remain uncertain. In this study, we demonstrated the cytocidal effects of DHTS on chemosensitive ovarian cancer cells with or without platinum-based chemotherapy. DHTS was able to inhibit proliferation and migration of ovarian cancer cells in vitro and in vivo through modulation of the PI3K/AKT signalling pathways. Combinatorial treatment of DHTS and cisplatin exhibited enhanced DNA damage in ovarian cancer cells. Overall, these findings suggest that DHTS induces ovarian cancer cells death via induction of DNA damage and inhibits ovarian cancer cell proliferation and migration.

Topics: Animals; Carcinoma, Ovarian Epithelial; Cell Death; Cell Line, Tumor; Cell Movement; Cell Proliferation; Class I Phosphatidylinositol 3-Kinases; Disease Models, Animal; Drug Resistance, Neoplasm; Female; Furans; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Ovarian Neoplasms; Phenanthrenes; Phosphatidylinositol 3-Kinases; Platinum; Proto-Oncogene Proteins c-akt; Quinones; Signal Transduction; Transcription, Genetic; Zebrafish

15,16-Dihydrotanshinone I (DHTS) is a component of the traditional Chinese medicinal plant Salvia miltiorrhiza Bunge. In this study, DHTS at as low as 2.5 μg/ml concentration significantly inhibited proliferation of human benign (SW480) and malignant (SW620) colorectal cancer cells, as shown by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) and flow cytometric analysis. Activating transcription factor (ATF)-3, a basic leucine zipper-type transcription factor, was found to be predominantly up-regulated in DHTS-treated SW480 and SW620 cells. The up-regulation of ATF3 was blocked by a c-JUN N-terminal kinase (JNK) or p38 inhibitor. Overexpression of ATF3 resulted in a significant augmentation of DHTS-induced apoptosis of SW480 cells, but resistance to DHTS-induced apoptosis of SW620 cells. These results suggest that DHTS has a strong therapeutic or preventive potential against cancer. In addition, ATF3 has a dual role in DHTS-induced apoptosis, depending on the degree of malignancy of colorectal cancer.

Topics: Activating Transcription Factor 3; Adenocarcinoma; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Drug Screening Assays, Antitumor; Furans; Humans; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Neoplasm Metastasis; Phenanthrenes; Phosphorylation; Quinones