Antitumor activity of RT2 peptide derived from crocodile leukocyte peptide on human colon cancer xenografts in nude mice

• Published in: Environmental toxicology Vol. 33; no. 9; pp. 972 - 977
• Main Authors: Maraming, Pornsuda, Klaynongsruang, Sompong, Boonsiri, Patcharee, Maijaroen, Surachai, Daduang, Sakda, Chung, Jing‐Gung, Daduang, Jureerut
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.09.2018; Wiley Subscription Services, Inc
• Subjects: Adenosine diphosphate; ADP; Alligators and Crocodiles; Animals; Anticancer properties; antineoplastic activity; Antineoplastic Agents - pharmacology; Antitumor activity; Antitumour agents; Apoptosis; Apoptosis - drug effects; Apoptosis-inducing factor; Aquatic reptiles; Body weight; Cancer; Cells; Cervical cancer; Cervix; Colon; Colon cancer; Colorectal cancer; colorectal neoplasms; crocodiles; Crocodylus siamensis; HCT116 Cells; hematologic tests; Hematology; Heterografts; Humans; Implantation; In vivo methods and tests; Leukocytes; Leukocytes - metabolism; Male; Mice; Mice, Inbred BALB C; Mice, Nude; NAD ADP-ribosyltransferase; neoplasm cells; Neoplasm Transplantation; Neoplasms; Oligopeptides - pharmacology; p53 Protein; Peptides; Phosphates; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases - metabolism; protein synthesis; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Ribose; RT2 peptide; Surgical implants; Tumor Burden; Tumor suppressor genes; tumor suppressor protein p53; Tumor Suppressor Protein p53 - metabolism; Tumors; uterine cervical neoplasms; xenograft; Xenografts; Xenotransplantation; RT2 peptide; apoptosis; colorectal cancer; xenograft; antitumor activity
• ISSN: 1520-4081; 1522-7278; 1522-7278
• DOI: 10.1002/tox.22584

RT2, derived from the leukocyte peptide of Crocodylus siamensis, can kill human cervical cancer cells via apoptosis induction, but no evidence has shown in vivo. In this study, we investigated the antitumor effect of RT2 on human colon cancer xenografts in nude mice. Twenty‐four mice were injected subcutaneously with human colon cancer HCT 116 cells. Eleven days after cancer cell implantation, the mice were treated with intratumoral injections of phosphate buffered saline (PBS) or RT2 (0.01, 0.1, and 1 mg/mouse) once every 2 days for a total of 5 times. The effect of a 10‐day intratumoral injection of RT2 on body weight, biochemical, and hematological parameters in BALB/c mice showed no significant difference between the groups. Tumor volume showed a significant decrease only in the treatment group with RT2 (1 mg/mouse) at day 6 (P < .05), day 8 (P < .01), and day 10 (P < .01) after the first treatment. The protein expression levels of cleaved poly (ADP‐ribose) polymerase (PARP), apoptosis‐inducing factor (AIF), and the p53 tumor suppressor protein (p53) in xenograft tumors increased after treatment with RT2 (1 mg/mouse) compared to those in the PBS‐injected group. Moreover, RT2 increased the expression of Endo G and Bcl‐2 family proteins. Therefore, the peptide RT2 can inhibit tumor growth via the induction of apoptosis in an in vivo xenograft model.