Background
AKT inhibitor VIII is a cell-permeable, reversible and potent, selective inhibitor of Akt1, Akt2 and Akt3 with IC50 values of 58 nM, 210 nM and 2.12 μM, respectively.
AKT inhibitor VIII has shown to remarkably increase anti-proliferation induced by furanodiene in human breast cancer cell MCF-7. AKT inhibitor VIII could enhance the furanodiene- stimulated Akt and p-Akt expression decreases as well as increase furanodiene-induced PARP cleavage in MCF-7 cells [1].
AKT inhibitor VIII has been revealed to inhibit IGF-1-induced Akt phosphorylation in a concentration-dependent manner. AKT inhibitor VIII has also been demonstrated to reduce PRAS40 phosphorylation in PC12 cells [2].
Reference:
[1] Zhong Z1, Dang Y, Yuan X, Guo W, Li Y, Tan W, Cui J, Lu J, Zhang Q, Chen X, Wang Y.? Furanodiene, a natural product, inhibits breast cancer growth both in vitro and in vivo. Cell Physiol Biochem. 2012;30(3):778-90.
[2] Wang H1, Zhang Q, Zhang L, Little PJ, Xie X, Meng Q, Ren Y, Zhou L, Gao G, Quirion R, Zheng W.? Insulin-like growth factor-1 induces the phosphorylation of PRAS40 via the PI3K/Akt signaling pathway in PC12 cells. Neurosci Lett. 2012 May 10;516(1):105-9.
Protocol
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Cell experiment [1]:
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Cell lines
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MCF-7 cell lines
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Preparation method
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The solubility of this compound in DMSO is >9.2 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
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Reacting condition
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10-100 μM for 24, 48, and 72 h
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Applications
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AKT inhibitor VIII significantly inhibited the proliferation and increased the LDH release in both cell lines in a dose-dependent manner. AKT inhibitor VIII dose-dependently induced cell cycle arrest at the G0/G1 phase. The protein expressions of p-cyclin D1, total cyclin D1, p-CDK2, total CDK2, pRb, total Rb, Bcl-xL, and Akt were significantly inhibited by AKT inhibitor VIII, whereas the protein expressions of Bad and Bax, and the proteolytic cleavage of caspase-9, caspase-7, and polyADP-ribose polymerase (PARP) were dramatically increased.
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Animal experiment [1]:
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Animal models
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BALB/c nude mice
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Dosage form
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15 mg/kg and 30 mg/kg by intraperitoneal administration once daily for 8 days
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Application
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AKT inhibitor VIII dose-dependently suppressed the tumor growth in vivo, achieving 32% and 54% inhibition rates after intraperitoneal injection of 15 mg/kg and 30 mg/kg, respectively.
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Other notes
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Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
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参考文献:
[1] [1] Zhong Z, Dang Y, Yuan X, Guo W, Li Y, Tan W, Cui J, Lu J, Zhang Q, Chen X, Wang Y. Furanodiene, a natural product, inhibits breast cancer growth both in vitro and in vivo. Cell Physiol Biochem. 2012;30(3):778-90.
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