BH3-based fusion artificial peptide induces apoptosis and targets human colon cancer.
Dysregulation of apoptosis is a pilot event before cancer development and plays important roles for cancer to develop resistance to chemical therapeutics. So exploring strategies to recovery the apoptosis balance is a charming and long-endeavored aim in the attempts to conquer cancers. The present study shows an exciting potency of a fusion peptide to inhibit and target to cancer cells, which is composed of BH3 (Bcl-2 Homology 3) effector domain from PUMA (p53 upregulated modulator of apoptosis) and targeting domain of trans-activator of transcription (TAT) and DV3. The in vitro results demonstrated cancer growth inhibition by the fusion peptide in colon cancer cells, as well as in lung adenocarcinoma cell line and breast carcinoma cell line of human origin. But the viability of HEK293, a noncancerous cell line, was not affected, indicating the cancer specificity of the fusion peptide. Apoptosis activation was induced by the peptide through the mitochondria pathway. In vivo studies displayed its tumor inhibiting ability by intratumoral injection. When the fusion peptide was administered systematically by tail vein, the peptide targeted the established tumors in nude mice. No other organs were significantly involved. The fusion peptide is an artificially designed molecule worthy of further evaluation and development.
State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China.
Yongjun
Y
Liu
Yunfeng
Y
Li
Haijuan
H
Wang
Jing
J
Yu
Hongwei
H
Lin
Dongkui
D
Xu
Yang
Y
Wang
Ailing
A
Liang
Xiao
X
Liang
Xueyan
X
Zhang
Ming
M
Fu
Haili
H
Qian
Chen
C
Lin
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005260:Female; D005434:Flow Cytometry; D015696:Gene Products, tat / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D015696:Gene Products, tat; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins