1. Academic Validation
  2. LvHemB1, a novel cationic antimicrobial peptide derived from the hemocyanin of Litopenaeus vannamei, induces cancer cell death by targeting mitochondrial voltage-dependent anion channel 1

LvHemB1, a novel cationic antimicrobial peptide derived from the hemocyanin of Litopenaeus vannamei, induces cancer cell death by targeting mitochondrial voltage-dependent anion channel 1

  • Cell Biol Toxicol. 2022 Feb;38(1):87-110. doi: 10.1007/s10565-021-09588-y.
Shangjie Liu 1 2 3 Jude Juventus Aweya 1 3 Liyuan Zheng 1 3 Zhou Zheng 1 3 He Huang 1 3 Fan Wang 1 3 Defu Yao 1 3 Tong Ou 4 Yueling Zhang 5 6
Affiliations

Affiliations

  • 1 Institute of Marine Sciences and Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, 515063, China.
  • 2 Institute of Urology, The Affiliated Shenzhen Luohu Hospital of Shantou University Medical College, Shantou University, Shantou, 515063, China.
  • 3 STU-UMT Joint Shellfish Research Laboratory, Shantou University, Shantou, 515063, China.
  • 4 Institute of Urology, The Affiliated Shenzhen Luohu Hospital of Shantou University Medical College, Shantou University, Shantou, 515063, China. ot81061017@163.com.
  • 5 Institute of Marine Sciences and Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, 515063, China. zhangyl@stu.edu.cn.
  • 6 STU-UMT Joint Shellfish Research Laboratory, Shantou University, Shantou, 515063, China. zhangyl@stu.edu.cn.
Abstract

Current Cancer treatment regimens such as chemotherapy and traditional chemical drugs have adverse side effects including the appearance of drug-resistant tumor cells. For these reasons, it is imperative to find novel therapeutic agents that overcome these factors. To this end, we explored a cationic antimicrobial peptide derived from Litopenaeus vannamei hemocyanin (designated LvHemB1) that induces Cancer cell death, but sparing normal cells. LvHemB1 inhibits the proliferation of human cervical (HeLa), esophageal (EC109), hepatocellular (HepG2), and bladder (EJ) Cancer cell lines, but had no significant effect on normal liver cell lines (T-antigen-immortalized human liver epithelial (THLE-3) cells). In addition to its antiproliferative effects, LvHemB1 induced Apoptosis, by permeating cells and targeting mitochondrial voltage-dependent anion channel 1 (VDAC1). Colocalization studies revealed the localization of LvHemB1 in mitochondria, while molecular docking and pull-down analyses confirmed LvHemB1-VDAC1 interaction. Moreover, LvHemB1 causes loss in mitochondrial membrane potential and increases levels of Reactive Oxygen Species (ROS) and apoptotic proteins (caspase-9, Caspase-3, and Bax (Bcl-2-associated X)), which results in mitochondrial-mediated Apoptosis. Thus, peptide LvHemB1 has the potential of being used as an Anticancer agent due to its antiproliferation effect and targeting to VDAC1 to cause mitochondrial dysfunction in Cancer cells, as well as its ability to induce Apoptosis by increasing ROS levels, and the expression of proapoptotic proteins.

Keywords

Anticancer; Antiproliferative effect; Apoptosis; Cationic antimicrobial peptide; Litopenaeus vannamei hemocyanin; Mitochondrial dysfunction.

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