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

Abstract

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.

Potential of crocodile blood as a medication and dietary supplement: A systemic review

“…Intratumoral injection of KT2 for 8 days 51 and RT2 for 10 days 53 did not affect the mouse body weight, while significantly reducing the volume and weight of the colon cancer xenografts, suggesting that KT2 and RT2 possess tumour‐selectivity in vivo .…”

“…KT2 and RT2, the two synthetic AMPs mentioned in “Novel Substances in Crocodile Blood”, were also suggested to not only induce cancer cell deaths in HeLa, CaSki (cervical cancer cell line), and HCT‐116 cells (colon cancer cell line) 23,54,55 but to also inhibit the migration and colony formation of HCT‐116 cells 54 . Following internalization, the AMPs led to downregulation of anti‐apoptotic genes, upregulation of pro‐apoptotic genes, release of cytochrome c, and activation of caspases in the cancer cells 51,53‐55 . In addition, KT2 also killed cancer cells by disrupting the cancer cell membrane lipids and increasing the membrane permeability 55 .…”

“…The organs of crocodiles, including the bile, liver, lung, gall bladder, heart, lungs, intestine, and brain, have been suggested to have antimicrobial and antitumour effects 16‐19 . As a primary transport medium supporting all the body parts, it is believed that crocodile blood holds the key for the maintenance of health and metabolic balance, leading to a lot of studies on its effects on microbial infection, 16,20‐36 viral infection, 37 inflammation, 26,38‐44 oxidation, 25,27,38,39,41,43‐47 tumors, 16,23,48‐55 wound healing, 22,25 and iron‐deficiency anaemia 56…”

Crocodile blood supplementation protects vascular function in diabetic mice

“…Crocodile blood, marketed as a dietary supplement since 2008 (Chaeychomsri et al 2013 ), has been suggested to have a wide range of physiological benefits (Chook et al 2021 ), including anti-oxidative (Jangpromma et al 2018 ; Lueangsakulthai et al 2018 ; Phosri et al 2014 , 2017 ; Theansungnoen et al 2014 ), anti-inflammatory (Jangpromma et al 2017 ; Kommanee et al 2014 ; Lueangsakulthai et al 2018 ; Pata et al 2011 ; Phosri et al 2014 , 2017 ), anti-microbial (Aree et al 2011 ; Hao et al 2012 ; Kommanee et al 2012 ; Merchant et al 2011 ; Pata et al 2007 , 2011 ; Phupiewkham et al 2018 ), anti-viral (Kozlowski et al 2016 ), anti-tumor (Maijaroen et al 2018 ; Maraming et al 2018 ; Ou & Ho 2016 ; Patathananone et al 2015 ; Phosri et al 2018 ), wound healing enhancing (Jangpromma et al 2016 ; Pakdeesuwan et al 2017 ) and anti-anemia (Chaeychomsri 2015 ) effects. Novel functional substances such as Leucrocins (Pata et al 2011 ) and crocosin (Preecharram et al 2010 ) were identified from crocodile blood.…”

Novel peptides with HIV‐1 reverse transcriptase inhibitory activity derived from the fruits of Quercus infectoria

“…Sompong's group hydrolysate previously evaluated the activity of the RT2 peptide derived from crocodile leukocyte peptide. They showed that better activity was derived from short antibacterial peptides and modifications than precursor or crude supernatant from living things (Anunthawan et al., 2013; Maraming et al., 2018; Pata et al., 2011).…”