| Description: |
Sinomenine HCl is a blocker of the NF-κB activation and also an activator of μ-opioid receptor, which has antiarrhythmic, anti-inflammatory, anti-tumor, and neuroprotective effects. Sinomenine HCl can improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities, it induces breast cancer cell death through ROS-dependent and -independent pathways with an upregulation of MAPKs.
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| Targets: |
ERK | JNK | p38MAPK | ROS | Chk | ATM/ATR | COX | VEGFR |
| In vitro: |
| Cell Death Dis. 2014 Jul 31;5:e1356. | | MAPK signaling mediates sinomenine hydrochloride-induced human breast cancer cell death via both reactive oxygen species-dependent and -independent pathways: an in vitro and in vivo study.[Pubmed: 25077542] | Sinomenine, the main alkaloid extracted from the medicinal plant Sinomenium acutum, is known for its anti-inflammatory effects. Recent studies have suggested its anti-cancer effect in synovial sarcoma, lung cancer and hepatic cancer. However, the underlying molecular mechanism for its anti-cancer effect still remains unclear.
METHODS AND RESULTS:
This study investigated the anti-tumor activity of sinomenine hydrochloride (Sinomenine HCl, SH), a hydrochloride form of sinomenine, in human breast cancer cells in vitro and in vivo. We found that SH potently inhibited cell viability of a broad panel of breast cancer cell lines. Two representative breast cancer cell lines, namely ER(-)/PR(-) MDA-MB-231 and ER(+)/PR(+) MCF-7, were used for further investigation. The results showed that SH induced G1/S cell cycle arrest, caused apoptosis and induced ATM/Chk2- and ATR/Chk1-mediated DNA-damage response in MDA-MB-231 and MCF-7. The anti-cancer effect of SH was regulated by increased expression levels of p-ERK, p-JNK and p-38 MAPK. Further studies showed that SH resulted in an increase in reactive oxygen species (ROS) and inhibition of ROS by N-acetyl-L-cysteine (NAC) almost blocked SH-induced DNA damage but only mitigated SH-induced MAPK expression changes, suggesting that both ROS-dependent and -independent pathways were involved in MAPK-mediated SH-induced breast cancer cell death. The in vivo study demonstrated that SH effectively inhibited tumor growth without showing significant toxicity.
CONCLUSIONS:
In conclusion, SH induced breast cancer cell death through ROS-dependent and -independent pathways with an upregulation of MAPKs, indicating that SH may be a potential anti-tumor drug for breast cancer treatment. |
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| In vivo: |
| Acta Pharmaceutica Sinica, 1985, 20(11):856-8. | | Anti-arrhythmic effects of sinomenine hydrochloride[Reference: WebLink] |
METHODS AND RESULTS:
Pretreatment of rats with sinomenine(Sinomenine HCl) 10～20 mg/kg iv significantly delayed the appearence and reduced the percentage of arrhythmia induced by aconitine 20 μg/kg iv. This alkaloid given 20 mg/kg iv increased the amount of ouabain required to produce ventricular premature beats and cardiac arrest in guinea pigs. while 20 mg/kg ip significantly reduced the incidence of ventricular fibrillation induced by chloroform inhalation in mice.
CONCLUSIONS:
In aneasthetized rats, sinomenine 20 mg/kg iv reduced the incidence of ventricular fibrillation and the mortality rate induced by iv CaCl_2 130 mg/kg. It might also abolish the arrhythmia induced by chloroform-adrenaline in rabbits. |
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