Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1
BackgroundThe human liver-related putative tumor 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.MethodsWe statisti...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1643155/full |
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| author | Hongchang Zhou Xiaoying Zhang Yao Wang Yongqiang Wu Ling Wang Chen Hu Ting Zhang Hui Zhang Dian You Mengli Zhao Mujun Zhao Anqi Li Guangming Chen |
| author_facet | Hongchang Zhou Xiaoying Zhang Yao Wang Yongqiang Wu Ling Wang Chen Hu Ting Zhang Hui Zhang Dian You Mengli Zhao Mujun Zhao Anqi Li Guangming Chen |
| author_sort | Hongchang Zhou |
| collection | DOAJ |
| description | BackgroundThe human liver-related putative tumor 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.MethodsWe statistically analyzed 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 analyzed in vitro and in vivo.ResultsThe 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.ConclusionsThe 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. |
| format | Article |
| id | doaj-art-7c13e41e10d644df89d77bb2e9d53820 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-7c13e41e10d644df89d77bb2e9d538202025-08-20T03:05:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.16431551643155Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1Hongchang Zhou0Xiaoying Zhang1Yao Wang2Yongqiang Wu3Ling Wang4Chen Hu5Ting Zhang6Hui Zhang7Dian You8Mengli Zhao9Mujun Zhao10Anqi Li11Guangming Chen12Huzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, Huzhou University, Huzhou, ChinaHuzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, Huzhou University, Huzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Huzhou University, Huzhou, ChinaBotuvac Biotechnology Co., Ltd, Beijing, ChinaBotuvac Biotechnology Co., Ltd, Beijing, ChinaHuzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, Huzhou University, Huzhou, ChinaHuzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, Huzhou University, Huzhou, ChinaHuzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, Huzhou University, Huzhou, ChinaHuzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, Huzhou University, Huzhou, ChinaHuzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, Huzhou University, Huzhou, ChinaThe Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, ChinaHuzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, Huzhou University, Huzhou, ChinaHuzhou Key Laboratory of Precise Prevention and Control of Major Chronic Diseases, School of Medicine, Huzhou University, Huzhou, ChinaBackgroundThe human liver-related putative tumor 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.MethodsWe statistically analyzed 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 analyzed in vitro and in vivo.ResultsThe 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.ConclusionsThe 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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1643155/fullLPTSTPCHtelomerasetelomerase inhibitorcancer |
| spellingShingle | Hongchang Zhou Xiaoying Zhang Yao Wang Yongqiang Wu Ling Wang Chen Hu Ting Zhang Hui Zhang Dian You Mengli Zhao Mujun Zhao Anqi Li Guangming Chen Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1 Frontiers in Oncology LPTS TPCH telomerase telomerase inhibitor cancer |
| title | Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1 |
| title_full | Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1 |
| title_fullStr | Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1 |
| title_full_unstemmed | Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1 |
| title_short | Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1 |
| title_sort | broad spectrum antitumor analysis of the telomerase activity inhibitor tpch derived from the human constitutively expressed protein lpts pinx1 |
| topic | LPTS TPCH telomerase telomerase inhibitor cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1643155/full |
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