Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model.
Crocetin, a carotenoid compound derived from saffron, has long been used as a traditional ancient medicine against different human diseases including cancer. The aim of the series of experiments was to systematically determine whether crocetin significantly affects pancreatic cancer growth both in vitro and/or in vivo. For the in vitro studies, first, MIA-PaCa-2 cells were treated with crocetin and in these sets of experiments, a proliferation assay using H(3)-thymidine incorporation and flow cytometric analysis suggested that crocetin inhibited proliferation. Next, cell cycle proteins were investigated. Cdc-2, Cdc-25C, Cyclin-B1, and epidermal growth factor receptor were altered significantly by crocetin. To further confirm the findings of inhibition of proliferation, H(3)-thymidine incorporation in BxPC-3, Capan-1, and ASPC-1 pancreatic cancer cells was also significantly inhibited by crocetin treatment. For the in vivo studies, MIA-PaCa-2 as highly aggressive cells than other pancreatic cancer cells used in this study were injected into the right hind leg of the athymic nude mice and crocetin was given orally after the development of a palpable tumor. The in vivo results showed significant regression in tumor growth with inhibition of proliferation as determined by proliferating cell nuclear antigen and epidermal growth factor receptor expression in the crocetin-treated animals compared with the controls. Both the in vitro pancreatic cancer cells and in vivo athymic nude mice tumor, apoptosis was significantly stimulated as indicated by Bax/Bcl-2 ratio. This study indicates that crocetin has a significant antitumorigenic effect in both in vitro and in vivo on pancreatic cancer.
Dhar
Animesh
A
Hematology and Oncology, University of Kansas Medical Center, Kansas City, Kansas, USA. adhar@kumc.edu
Mehta
Smita
S
Dhar
Gopal
G
Dhar
Kakali
K
Banerjee
Snigdha
S
Van Veldhuizen
Peter
P
Campbell
Donald R
DR
Banerjee
Sushanta K
SK
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D066246:ErbB Receptors