Cancer: Breast, ovarian
Action: Multi-drug resistance, anti-inflammatory, blocks neurotoxicity
Mollugin originally isolated from Rubia cordifolia (L.) is a pharmacological compound for its anti-inflammation, anti-cancer, and anti-viral activity. Mollugin-caused inhibition of phenacetin O-deethylation was concentration-dependent in hierarchical linear models (HLMs), but not time-dependent. In addition, the Lineweaver-Burk plot indicated a typical competitive inhibition. Inhibitory effects of mollugin on human recombinant cDNA-expressed CYP1A1 and 1A2 were comparable. Taken together, the results suggested that mollugin might cause herb-drug interaction through selective inhibition of CYP1A2 in humans receiving herbal medications, including R. cordifolia (Kim et al., 2013).
MDR, Anti-inflammatory
Mollugin treatment significantly inhibited MDR1 expression by blocking MDR1 transcription. P-glycoprotein (P-gp), an important efflux transporter, is encoded by the MDR1 class of genes and is a central element of the multi-drug resistance (MDR) phenomenon in cancer cells. The suppression of MDR1 promoter activity and protein expression was mediated through mollugin-induced activation of AMP-activated protein kinase (AMPK). Furthermore, mollugin inhibited MDR1 expression through the suppression of NF-κB and cAMP-response element binding protein (CREB) activation. These results suggest that mollugin treatment enhanced suppression of P-gp expression by inhibiting the NF-κB signaling pathway and COX-2 expression, as well as attenuating cAMP-response element (CRE) transcriptional activity through AMPK activation (Tran et al., 2013).
Breast Cancer; Ovarian Cancer
Mollugin exhibited potent inhibitory effects on cancer cell proliferation, especially in HER2-overexpressing SK-BR-3 human breast cancer cells and SK-OV-3 human ovarian cancer cells in a dose- and time-dependent manner without affecting immortalized normal mammary epithelial cell line MCF-10A. Mollugin treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF-κB activation. The combination of mollugin with a MEK1/2 inhibitor may be required in order to achieve optimal efficacy in HER2-overexpressing cancers.
These findings suggest that mollugin is a novel modulator of the HER2 pathway in HER2-overexpressing cancer cells with a potential role in the treatment and prevention of human breast and ovarian cancer with HER2 overexpression (Do et al., 2013).
Blocks Neurotoxicity, Anti-inflammatory
Mollugin also has effects as a neuro-protective agent in glutamate-induced neurotoxicity in the mouse hippocampal HT22 cell line and as an anti-inflammatory agent in lipopolysaccharide-induced microglial activation in BV2 cells. Mollugin showed potent neuro-protective effects against glutamate-induced neuro-toxicity and reactive oxygen species generation in mouse hippocampal HT22 cells.
In addition, the anti-inflammatory effects of mollugin were demonstrated by the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-6). Furthermore, mollugin also activated the p38 mitogen-activated protein kinase (MAPK) pathway both in HT22 and BV2 cells. These results suggest that mollugin may be a promising candidate for the treatment of neurodegenerative diseases related to neuroinflammation (Jeong et al., 2011).
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