Shrimp anti-lipopolysaccharide factor peptide enhances the antitumor activity of cisplatin in vitro and inhibits HeLa cells growth in nude mice.
The antitumor activity of the shrimp anti-lipopolysaccharide factor (SALF), an antimicrobial peptide, was not previously examined. In this study, a synthetic SALF was tested for antitumor activity using HeLa cells as the study model. We show that the SALF inhibited the proliferation of HeLa cells and reduced colony formation in a soft agar assay. An enhanced effect was observed when the SALF and cisplatin were used in combination, which caused significant inhibition of HeLa cells. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the SALF altered the membrane structure similar to what a lytic peptide does. A flow cytometric analysis, qRT-PCR, and Western blotting showed that the SALF induced apoptosis, activated caspases-6, -7, and -9, and downregulated Bcl-2 and nuclear factor (NF)-kappaB suggesting that the SALF induces apoptosis through the death receptor/NF-kappaB signaling pathway. An in vivo analysis revealed that the SALF displayed significant tumor suppressive activity in mice with tumor xenografts. Overall, these results indicated that the SALF possesses the potential to be a novel therapeutic agent for treating cervical cancer.
Lin
Ming-Ching
MC
Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan 262, Taiwan.
Lin
Shih-Bin
SB
Chen
Jian-Chyi
JC
Hui
Cho-Fat
CF
Chen
Jyh-Yih
JY
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D060829:Arthropod Proteins; D020169:Caspases / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000494:pharmacology*
D000970:Antineoplastic Agents; D060829:Arthropod Proteins; D010446:Peptide Fragments; C520222:shrimp anti-lipopolysaccharide factor cyclic peptide (55-76); D020169:Caspases; D002945:Cisplatin