Antiproliferative Activity of Crocin Involves Targeting of Microtubules in Breast Cancer Cells.
Crocin, a component of saffron spice, is known to have an anticancer activity. However, the targets of crocin are not known. In this study, crocin was found to inhibit the proliferation of HCC70, HCC1806, HeLa and CCD1059sk cells by targeting microtubules. Crocin depolymerized both the interphase and mitotic microtubules of different cancer cells, inhibited mitosis and induced multipolar spindle formation in these cells. In vitro, crocin inhibited the assembly of pure tubulin as well as the assembly of microtubule-associated protein rich tubulin. Electron microscopic analysis showed that crocin inhibited microtubule assembly while it induced aggregation of tubulin at higher concentrations. Crocin co-eluted with tubulin suggesting that it binds to tubulin. Vinblastine inhibited the binding of crocin to tubulin while podophyllotoxin did not inhibit the crocin binding indicating that crocin binds at the vinblastine site on tubulin. The results suggested that crocin inhibited cell proliferation mainly by disrupting the microtubule network.
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 India.|Department of Genetics, University of Georgia, Athens, Georgia 30602 USA.
Rupali R
RR
Hire
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 India.
Shalini
S
Srivastava
Department of Genetics, University of Georgia, Athens, Georgia 30602 USA.
Melissa B
MB
Davis
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 India.|Department of Biomedical &Pharmaceutical Sciences, University of Georgia College of Pharmacy, Athens, Georgia 30602 USA.
Ananda
A
Kumar Konreddy
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 India.
Dulal
D
Panda
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism / Q000648:ultrastructure; D050257:Tubulin Modulators / Q000494:pharmacology
D000970:Antineoplastic Agents; D014404:Tubulin; D050257:Tubulin Modulators; D002338:Carotenoids; C029036:crocin