Thanasak Jitkamol, Roytrakul Sittiruk, Surarit Rudee, Toniti Waraphan, Sirimanapong Wanna, Jaresitthikunchai Janthima, Phaonakrop Narumon, Thaisakun Siriwan, Charoenlappanit Sawanya, Jittakhot Surasak
Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand.
Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand.
PLoS One. 2025 Apr 17;20(4):e0321531. doi: 10.1371/journal.pone.0321531. eCollection 2025.
This study investigated the anticancer efficacy of <3 kDa fractions derived from native peptides and protein hydrolysate of Varanus saltator serum. The inhibitory effects of these fractions were evaluated against a panel of cancer cell lines (A375, CaCO2, CAL27, NCI-H460, HeLa, HCT8, HT29, HepG2, KATO III, MCF-7, MDA-MB-231, Raw264.7, SKOV-3, SW620, T47D, and U937) and normal cell lines (HaCaT, MRC5, and Vero). Native peptides demonstrated higher anticancer activity compared to protein hydrolysates, inhibiting 16 cell lines and exhibiting high efficacy (≥70% inhibition) against CaCO2, CAL27, HaCaT, HT29, HepG2, MCF-7, MRC5, and U937. These native peptides were further fractionated by stepwise reverse-phase column chromatography. The hydrophilic (C18 unbound) peptide fraction exhibited greater anticancer activity than the hydrophobic (C18 bound) fraction. In addition, by LC-MS analysis, the peptide sequences were screening in silico. The predictions showed that 159 of the 432 Varanus peptides had the potential to be anticancer peptides (ACPs), of which the top twenty had a probability of more than 75%. The anticancer mechanism of peptides may be explained by the mechanism of cell entry or action. Further peptide synthesis and modification should be the next step to enhance the anticancer efficacy of these peptides with less toxicity to Vero cells. This finding sets the way for the development of new anticancer drugs originating from Varanus salvator serum peptides.
本研究调查了源自圆鼻巨蜥血清天然肽和蛋白质水解产物的<3 kDa组分的抗癌功效。评估了这些组分对一组癌细胞系（A375、CaCO2、CAL27、NCI-H460、HeLa、HCT8、HT29、HepG2、KATO III、MCF-7、MDA-MB-231、Raw264.7、SKOV-3、SW620、T47D和U937）和正常细胞系（HaCaT、MRC5和Vero）的抑制作用。与蛋白质水解产物相比，天然肽表现出更高的抗癌活性，抑制了16种细胞系，并对CaCO2、CAL27、HaCaT、HT29、HepG2、MCF-7、MRC5和U937表现出高效（≥70%抑制）。这些天然肽通过逐步反相柱色谱进一步分离。亲水性（未结合C18）肽组分比疏水性（结合C18）组分表现出更大的抗癌活性。此外，通过液相色谱-质谱分析，对肽序列进行了计算机筛选。预测显示，432种圆鼻巨蜥肽中有159种有潜力成为抗癌肽（ACP），其中前二十种的概率超过75%。肽的抗癌机制可能通过细胞进入或作用机制来解释。进一步的肽合成和修饰应该是下一步，以提高这些肽的抗癌功效，同时对Vero细胞的毒性更小。这一发现为开发源自圆鼻巨蜥血清肽的新型抗癌药物铺平了道路。
