title: TMPyP4 promotes cancer cell migration at low doses, but induces cell death at high doses.
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.
authors.affiliation: Medical School, Shenzhen University, Shenzhen 518060, P. R. China.|Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China.|Collaborative Innovation Center of High Performance Computing, National University of Defense Technology, Changsha 410073, P. R. China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China.|Collaborative Innovation Center of High Performance Computing, National University of Defense Technology, Changsha 410073, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Nie
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China.|Collaborative Innovation Center of High Performance Computing, National University of Defense Technology, Changsha 410073, P. R. China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China.|Collaborative Innovation Center of High Performance Computing, National University of Defense Technology, Changsha 410073, P. R. China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Fang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China.|Collaborative Innovation Center of High Performance Computing, National University of Defense Technology, Changsha 410073, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Medical School, Shenzhen University, Shenzhen 518060, P. R. China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Xia
mesh_terms: D000072283:A549 Cells; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011166:Porphyrins / Q000494:pharmacology*
chemical_list: D011166:Porphyrins; C021096:tetra(4-N-methylpyridyl)porphine