Chlorin p6 preferentially localizes in endoplasmic reticulum and Golgi apparatus and inhibits Ca(2+) release from intracellular store.
Subcellular localization of chlorin p6 in human cerebral glioma (U-87MG) cells was studied using laser scanning confocal microscopy. Localization in sub cellular organelles was ascertained by double labeling with specific fluorescent markers of subcellular organelles. The results reveal that chlorin p6 binds to multiple cellular sites but preferential binding sites are endoplasmic reticulum and Golgi apparatus and it does not bind to mitochondria. Significantly the drug localization pattern of proliferating and differentiated cells was notably distinct. In proliferating cells the internalization of drug was faster than in differentiated cells. Localization of chlorin p6 into the cells inhibited Ca(2+) release from endoplasmic reticulum and deregulated cellular Ca(2+) signalling. These results suggest that the fluorescence imaging pattern of chlorin p6 could be useful in identifying the proliferating and differentiated population of cells in tumor tissue.
Begum
Gulnaz
G
Department of Biophysics, National Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India.
Dube
Alok
A
Joshi
Preeti G
PG
Gupta
Pradeep K
PK
Joshi
Nanda B
NB
D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000378:metabolism; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry; D006056:Golgi Apparatus / Q000737:chemistry*; D006801:Humans; D018613:Microscopy, Confocal; D017319:Photosensitizing Agents / Q000032:analysis* / Q000494:pharmacology*; D011166:Porphyrins / Q000032:analysis* / Q000494:pharmacology*; D015398:Signal Transduction
D002120:Calcium Channel Agonists; D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011166:Porphyrins; C072905:chlorin p6; D002118:Calcium