Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells.

BACKGROUND: Honokiol is a natural polyphenolic compound extracted from Magnolia officinali, which is commonly used material in Chinese herbal medicine, has a variety of biological functions, including anti-tumor, anti-oxidant, anti-inflammation, anti-microbial and anti-allergy. Although honokiol has numerous beneficial effects on human diseases, the underlying mechanisms of tumor metastasis are still unclear. Previously, we reported that honokiol suppresses thyroid cancer cell proliferation with cytotoxicity through cell cycle arrest, apoptosis, and dysregulation of intracellular hemostasis. Herein, we hypothesized that the antioxidant effect of honokiol might play a critical role in thyroid cancer cell proliferation and migration. METHODS: The cell viability assays, cellular reactive oxygen species (ROS) activity, cell migration, and immunoblotting were performed after cells were treated with honokiol. RESULTS: Based on this hypothesis, we first demonstrated that honokiol suppresses cell proliferation in two human anaplastic thyroid carcinoma (ATC) cell lines, KMH-2 and ASH-3, within a dosage- and time-dependent manner by cell counting kit-8 (CCK-8) assay. Next, we examined that honokiol induced ROS activation and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC). Furthermore, the honokiol suppressed cell proliferation can be rescued by pre-treated with NAC. Finally, we demonstrated that honokiol inhibited ATC cell migration by modulating epithelial-mesenchymal transition (EMT)-related markers by Western blotting. CONCLUSION: Taken together, we provided the potential mechanism for treating ATC cells with honokiol, which significantly suppresses tumor proliferation and inhibits tumor metastasis in vitro through reactive oxygen species (ROS) induction.

Berberine Derivatives Suppress Cellular Proliferation and Tumorigenesis In Vitro in Human Non-Small-Cell Lung Cancer Cells.

Lung cancer is the leading cause of death in the world, and the most common type of lung cancer is non-small-cell lung cancer (NSCLC), accounting for 85% of lung cancer. Patients with NSCLC, when detected, are mostly in a metastatic stage, and over half of patients diagnosed with NSCLC die within one year after diagnosis; the 5-year survival rate is 24%. However, in patients with metastatic NSCLC, the 5-year survival rate is 6%. Therefore, development of a new therapeutic agent or strategy is urgent for NSCLCs. Berberine has been illustrated to be a therapeutic agent of NSCLC. In the present study, we synthesized six derivatives of berberine, and the anti-NSCLC activity of these agents was examined. Some of them exert increasing proliferation inhibition comparing with berberine. Further studies demonstrated that two of the most effective agents, 9-O-decylberberrubine bromide (B6) and 9-O-dodecylberberrubine bromide (B7), performed cell cycle regulation, in-vitro tumorigenesis inhibition and autophagic flux blocking, but not induction of cellular apoptosis in NSCLC cells. Moreover, B6 and B7 were determined to be green fluorescent and could be penetrated and localized in cellular mitochondria. Herein, B6 and B7, the berberine derivatives we synthesized, revealed better anti-NSCLC activity with berberine and may be used as therapeutic candidates for the treatment of NSCLCs.

Honokiol Is a Potential Therapeutic Agent and Has a Synergistic Effect With 5-FU in Human Urothelial Cell Carcinoma Cells.

BACKGROUND/AIM: Honokiol is a biphenolic component of the bark of Magnolia, and has been shown to exert several activities, including anti-depressant, anti-emetic, anti-oxidative, anti-thrombotic, anti-angiogenesis, anti-anxiolytic, anti-inflammatory and anti-tumor effects. MATERIALS AND METHODS: The anti-tumor activities of honokiol and its synergistic effect with 5-fluorouracil (5-FU) in human urothelial cell carcinoma (UCC) cells were investigated. RESULTS: Honokiol significantly suppressed the proliferation of UCC cells in a dose- and time-dependent manner. Moreover, honokiol inhibited the tumorigenesis of UCC cells in vitro. In addition, honokiol induced cell cycle arrest at G0/G1 phase and caused apoptosis of UCC cells through the intrinsic pathway. Importantly, we demonstrated that honokiol potentiated the cytotoxic effect of 5-FU, and displayed a synergistic effect with 5-FU in UCC cells. CONCLUSION: Honokiol causes growth inhibition, tumorigenesis suppression, cell cycle arrest, apoptosis, and importantly has a synergistic effect with 5-FU in human UCC cells. Therefore, this agent displays a therapeutic potential for treating human UCC.