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TMPyP4 promotes cancer cell migration at low doses, but induces cell death at high doses
Xiao-Hui Zheng1,2,3, Xin Nie2,3, Hai-Ying Liu2,3
1Medical School, Shenzhen University, Shenzhen 518060, P. R. China.
Abstract:
TMPyP4 is widely considered as a potential photosensitizer in photodynamic therapy and a G-quadruplex stabilizer for telomerase-based cancer therapeutics. However, its biological effects including a possible adverse-effect are poorly understood. In this study, whole genome RNA-seq analysis was used to explore the alteration in gene expression induced by TMPyP4. Unexpectedly, we find that 27.67% of changed genes were functionally related to cell adhesion. Experimental evidences from cell adhesion assay, scratch-wound and transwell assay indicate that TMPyP4 at conventional doses (≤0.5 μM) increases cell-matrix adhesion and promotes the migration of tumor cells. In contrast, a high dose of TMPyP4 (≥2 μM) inhibits cell proliferation and induces cell death. The unintended "side-effect" of TMPyP4 on promoting cell migration suggests that a relative high dose of TMPyP4 is preferred for therapeutic purpose. These findings contribute to better understanding of biological effects induced by TMPyP4 and provide a new insight into the complexity and implication for TMPyP4 based cancer therapy.
Insights
Tetrapyrrole macrocycle TMPyP4 shows dual effects in cancer therapy. Low doses promote tumor cell migration, while high doses inhibit proliferation and induce cell death, suggesting higher doses for therapeutic use.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Tetrapyrrole macrocycle TMPyP4 is investigated for photodynamic therapy and G-quadruplex stabilization in cancer treatment.
- The comprehensive biological effects and potential adverse effects of TMPyP4 remain incompletely understood.
Purpose of the Study:
- To investigate the gene expression alterations induced by TMPyP4 using whole genome RNA-seq.
- To elucidate the impact of TMPyP4 on cellular processes, particularly cell adhesion and migration.
Main Methods:
- Whole genome RNA-sequencing (RNA-seq) to analyze gene expression changes.
- Cell adhesion assays, scratch-wound assays, and Transwell assays to evaluate cell migration and proliferation.
Main Results:
- TMPyP4 significantly alters gene expression, with 27.67% of changed genes related to cell adhesion.
- Low doses (≤0.5 μM) of TMPyP4 enhance cell-matrix adhesion and promote tumor cell migration.
- High doses (≥2 μM) of TMPyP4 inhibit cell proliferation and induce cell death.
Conclusions:
- TMPyP4 exhibits dose-dependent effects on cancer cells, influencing both migration and viability.
- The promotion of cell migration at lower doses suggests a potential complication or a strategy for therapeutic application.
- Higher doses of TMPyP4 are indicated for therapeutic purposes due to their antiproliferative and cell-death-inducing effects, offering new insights into TMPyP4-based cancer therapy.
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