Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1.

BACKGROUND

The 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.

METHODS

We 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 and .

RESULTS

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 and inhibited the growth of MCF-7, A549 and SW480 cell line-derived xenograft (CDX) and liver cancer patient-derived xenograft (PDX) mouse models 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.

CONCLUSIONS

The TPCH protein strongly inhibited telomerase activity and suppressed the growth of all tested human telomerase-positive cancer cell lines and . Therefore, it could be developed as a broad-spectrum anticancer agent with low toxicity.