ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1643155
This article is part of the Research TopicInnovative Strategies for the Discovery of New Therapeutic Targets in Cancer TreatmentView all articles
Broad-spectrum antitumour analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1
Provisionally accepted
Hongchang Zhou1Xiaoying Zhang1Yao Wang2Yongqiang Wu3Ling Wang3Chen Hu1Ting Zhang1
Zhang Hui1Dian You1Mengli Zhao1Mujun Zhao4Anqi Li1
Guangming Chen1*- 1Huzhou University, Huzhou, China
- 2The First People's Hospital of Huzhou, Huzhou, China
- 3Botuvac Biotechnology Co Ltd, Beijing, China
- 4The institute of biochemistry and cell biology, Shanghai, China
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The human liver-related putative tumour suppressor LPTS/PinX1 is a gene encoding a telomerase inhibitory protein. Overexpression of LPTS/PinX1 protein can inhibit the growth of multiple telomerase-positive cancer cell lines. LPTS/PinX1 has therapeutic potential for cancer.We statistically analysed the level of LPTS/PinX1 protein in 9 cancer cell lines.LPTS/PinX1158-328 (exon 7 of LPTS) was fused with TAT to generate the recombinant protein TPCH. The effects of the TPCH protein on cell growth, senescence and apoptosis in 14 cell lines were analysed in vitro and in vivo.The purified TPCH protein was delivered into cells and inhibited telomerase activity. Also it inhibited the growth of 11 telomerase-positive cancer cell lines, was ineffective in 3 telomerase-negative cell lines in vitro and inhibited the growth of MCF-7, A549 and SW480 cell line-derived xenograft (CDX) and liver cancer patient-derived xenograft (PDX) mouse models in vivo. The inhibitory effect on the cancer cell growth was negatively correlated with the telomere length. The TPCH protein induced senescence and apoptosis in telomerase-positive cancer cells through the p21 signaling pathway and inhibited the migration of telomerase-positive cancer cells.The TPCH protein strongly inhibited telomerase activity and suppressed the growth of all tested human telomerase-positive cancer cell lines in vitro and in vivo. Therefore, it could be developed as a broad-spectrum anticancer agent with low toxicity.
Keywords: LPTs, TPCH, Telomerase, Telomerase Inhibitor, Cancer
Received: 08 Jun 2025; Accepted: 24 Jul 2025.
Copyright: © 2025 Zhou, Zhang, Wang, Wu, Wang, Hu, Zhang, Hui, You, Zhao, Zhao, Li and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Guangming Chen, Huzhou University, Huzhou, China
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