cytochrome-c-t and crocin

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.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Carotenoids; Cell Cycle Proteins; Cell Line, Tumor; Cell Survival; Crocus; Cytochromes c; Female; Humans; Lipid Peroxidation; Liver Diseases; Mice; Mice, Nude; Pancreatic Neoplasms; Radiation Injuries; Signal Transduction; Transcriptome; Xenograft Model Antitumor Assays

In this study, we want to understand whether crocin could prevent mitochondrial damage caused by As III. For this purpose, we determined different mitochondrial toxicity endpoints caused by As III. We evaluated mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential (MMP) collapse, mitochondrial outer membrane integrity and cytochrome c release. Our results showed that pretreatment with crocin at a concentration of 25 µg/ml significantly (p < 0.001) reduced As III-induced mitochondrial ROS formation, lipid peroxidation, MMP collapse and mitochondrial swelling. Crocin also protected the mitochondria by decreasing the mitochondrial outer membrane damage that leads to reduce the amount of cytochrome c release. These results demonstrated that crocin is a promising antidotal candidate by ameliorating As III-induced oxidative stress through mitochondrial targeting.

Topics: Animals; Arsenic; Carotenoids; Cytochromes c; Glutathione; Lipid Peroxidation; Male; Membrane Potential, Mitochondrial; Mitochondria, Liver; Mitochondrial Swelling; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

This study was designed to evaluate the effectiveness of crocin, main component of Crocus sativus L. (Saffron) against subchronic diazinon (DZN) induced cardiotoxicity in rats.. Rats were divided into 7 groups; control (corn oil, gavage), DZN (15 mg/kg/day, gavage,), crocin (12.5, 25 or 50 mg/kg/day, i.p) plus DZN, vitamin E (200 IU/kg, i.p, three times per week) plus DZN and crocin (50 mg/kg/day, i.p) groups. Treatments were continued for 4 weeks. Creatine phosphokinase MB (CK-MB), malondealdehyde (MDA) and glutathione (GSH) levels were evaluated in heart tissue at the end of treatments. Levels of apoptotic proteins (Bax, Bcl2, caspase 3) and cytosolic cytochrome c were analyzed by Western blotting. Transcript levels of Bax and Bcl2 were also determined using qRT PCR.. DZN induced histophatological damages and elevated the level of cardiac marker CK-MB. These effects were associated with increased MDA level, lower level of reduced GSH and induction of apoptosis through elevation of Bax/Bcl2 ratio (both protein and mRNA levels), cytochrome c release to the cytosol and activation caspase 3 in cardiac tissue. Crocin (25 and 50 mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN. In summary, DZN induced mitochondrial-mediated apoptosis in heart tissue of rat following subchronic exposure. Crocin, as an antioxidant, showed protective effects against DZN cardiotoxicity by reducing lipid peroxidation and alleviating apoptosis.

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Carotenoids; Creatine Kinase; Crocus; Cytochromes c; Diazinon; Disease Models, Animal; Gene Expression; Glutathione; Heart; Heart Diseases; Insecticides; Male; Malondialdehyde; Myocardium; Necrosis; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; RNA, Messenger

Platelets are the key players in the development of cardiovascular diseases as the microparticles generated by apoptotic platelets and platelet aggregation contribute actively towards the disease propagation. Thus, the aim of this study was to demonstrate the effect of a phytochemical which can prevent these two processes and thereby project it as a cardio-protective compound. Crocin, a natural carotenoid exhibits a wide spectrum of therapeutic potentials through its antioxidant property. The study demonstrated its effects on cytoplasmic apoptotic events of mitochondrial pathway in platelets. Collagen/calcium ionophore-A23187 stimulated platelets were treated with crocin and endogenous generation of reactive oxygen species (ROS) and hydrogen peroxide (H(2)O(2)) were measured. H(2)O(2)-induced changes in crocin-pretreated platelets such as intracellular calcium, mitochondrial membrane potential (ΔΨm), caspase activity, phosphatidylserine exposure and cytochrome c translocation were determined. Crocin dose-dependently ameliorated collagen- and A23187-induced endogenous generation of ROS and H(2)O(2). It also abolished the H(2)O(2)-induced events of intrinsic pathway of apoptosis. Further, it hindered collagen-induced platelet aggregation and adhesion. The current piece of work clearly suggests its anti-apoptotic effect as well as inhibitory effects on platelet aggregation. Thus, crocin can be deemed as a prospective candidate in the treatment regime of platelet-associated diseases.

Topics: Antioxidants; Apoptosis; Blood Platelets; Calcium Signaling; Carotenoids; Caspase 3; Caspase 9; Cell Adhesion; Cell Membrane; Cytochromes c; Enzyme Activation; Food Additives; Humans; Hydrogen Peroxide; Membrane Potential, Mitochondrial; Oxidative Stress; Phosphatidylserines; Platelet Aggregation; Platelet Aggregation Inhibitors