d-(KLAKLAK) 2, Proapoptotic Peptide acetate is a pro- Apoptotic peptide whose core mechanism of action is to disrupt organelle membranes, especially mitochondrial membranes, thereby inducing apoptosis. d-(KLAKLAK) 2, Proapoptotic Peptide acetate activates the activity of caspase 3/7 in cancer cells. Although d-(KLAKLAK) 2 Proapoptotic Peptide acetate exhibits very low toxicity to eukaryotic cells extracellularly, it cannot effectively penetrate cell membranes to enter the cytoplasm on its own. d-(KLAKLAK) 2, Proapoptotic Peptide acetate must be conjugated with a carrier capable of "homing" and "internalization" to exert its anti-cancer effects [1] [2].
In Vivo, Cationic liposomes co-loaded with d-(KLAKLAK)2, Proapoptotic Peptide acetate and G3139 (1.52 μg; intratumoral; twice daily, total 2 doses) deliver a 60% tumor growth inhibition in B16(F10) melanoma-bearing mice via enhanced apoptotic activity[1].
In Vitro, d-(KLAKLAK)2 (0.44 μM) acetate induces mitochondrial swelling in a cell-free system with an ED50 of 0.44 μM[1]. d-(KLAKLAK)2 (0.4 μM) acetate induces mitochondrial membrane potential loss in a cell-free system with an ED50 of 0.4 μM[1]. Cationic liposome-delivered d-(KLAKLAK)2 (co-loaded with G3139) (0.1875-1.5 μM; 24 h) acetate reduces viability of B16(F10) mouse melanoma cells by ~20% at 0.1875 μM and ~40% at 0.375 μM[1]. d-(KLAKLAK)2, Proapoptotic Peptide (24 hours) acetate does not inhibit proliferation of highly metastatic PC-3M-1E8 prostate cancer cells, MKN-45sci gastric cancer cells, or NIH/3T3 fibroblast cells[2]. d-(KLAKLAK)2, Proapoptotic Peptide acetate does not induce apoptosis in highly metastatic PC-3M-1E8 prostate cancer cells or MKN-45sci gastric cancer cells, as it cannot enter the tumor cells[2].
References:
[1]. Ko YT, et al. Cationic liposomes loaded with proapoptotic peptide D-(KLAKLAK)(2) and Bcl-2 antisense oligodeoxynucleotide G3139 for enhanced anticancer therapy. Mol Pharm. 2009 May-Jun;6(3):971-7.
[2]. Ma X, et al. Anti-tumor effects of the peptide TMTP1-GG-D(KLAKLAK)(2) on highly metastatic cancers. PLoS One. 2012;7(9):e42685.
In Vivo, Cationic liposomes co-loaded with d-(KLAKLAK)2, Proapoptotic Peptide acetate and G3139 (1.52 μg; intratumoral; twice daily, total 2 doses) deliver a 60% tumor growth inhibition in B16(F10) melanoma-bearing mice via enhanced apoptotic activity[1].
In Vitro, d-(KLAKLAK)2 (0.44 μM) acetate induces mitochondrial swelling in a cell-free system with an ED50 of 0.44 μM[1]. d-(KLAKLAK)2 (0.4 μM) acetate induces mitochondrial membrane potential loss in a cell-free system with an ED50 of 0.4 μM[1]. Cationic liposome-delivered d-(KLAKLAK)2 (co-loaded with G3139) (0.1875-1.5 μM; 24 h) acetate reduces viability of B16(F10) mouse melanoma cells by ~20% at 0.1875 μM and ~40% at 0.375 μM[1]. d-(KLAKLAK)2, Proapoptotic Peptide (24 hours) acetate does not inhibit proliferation of highly metastatic PC-3M-1E8 prostate cancer cells, MKN-45sci gastric cancer cells, or NIH/3T3 fibroblast cells[2]. d-(KLAKLAK)2, Proapoptotic Peptide acetate does not induce apoptosis in highly metastatic PC-3M-1E8 prostate cancer cells or MKN-45sci gastric cancer cells, as it cannot enter the tumor cells[2].
References:
[1]. Ko YT, et al. Cationic liposomes loaded with proapoptotic peptide D-(KLAKLAK)(2) and Bcl-2 antisense oligodeoxynucleotide G3139 for enhanced anticancer therapy. Mol Pharm. 2009 May-Jun;6(3):971-7.
[2]. Ma X, et al. Anti-tumor effects of the peptide TMTP1-GG-D(KLAKLAK)(2) on highly metastatic cancers. PLoS One. 2012;7(9):e42685.