Abstract
Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
Highlights
Pancreatic cancer has become the seventh-largest cause of cancer-related death by 2020 [1], with an expected 5-year survival rate of approximately 8% [2]
This alteration in the Bcl-2/Bax ratio indicates the apoptosis-inducing potential of crocin in BXPC3 and Capan-2 cells. This is in agreement with previous results [26,46,47,48], in which crocin is shown to affect the Bax/Bcl2 ratio to cause apoptosis in Leukemia, lung cancer, AGS gastric cancer and prostate cancer cells
Our data suggest that crocin could localize into the nucleus of BXPC3 and capan-2 cells and suppress the Myc expression. Consistent with this notion in the present study, we demonstrate that increased p53, p38, p21/p27 expression and downregulation of CDK2 and c-MYC levels could be an explanation by which BXPC3 and Capan-2 cells undergo cell cycle arrest during crocin exposure
Summary
Pancreatic cancer has become the seventh-largest cause of cancer-related death by 2020 [1], with an expected 5-year survival rate of approximately 8% [2]. It is the seventh leading cause of cancer-related mortality, causing over 300,000 deaths per year [3]. Treatment with chemotherapeutic agents is the mainstream option [6,7]. Sophisticated treatment options, such as those using targeted immunological therapies (vismodegib and erlotinib), have not proven successful to date [6]. Severe side effects limit the use of chemo-radiotherapy
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