Apoptotic death of pancreatic cancer cells induced by polyunsaturated fatty acids varies with double bond number and involves an oxidative mechanism

Hawkins, R. A.; Sangster, Kathryn; Arends, Mark J.

doi:10.1002/(sici)1096-9896(199805)185:1<61::aid-path49>3.0.co;2-8

Cited by 128 publications

(13 citation statements)

References 26 publications

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“…There is increasing evidence that they play an important role in cancer risk and progression. Many studies have been reported to demonstrate the effects of unsaturated fatty acids on the inhibition of cancer cells and the induction of cancer cell death . Among them, ω‐HUA, a plant secondary metabolite showing anti‐fungal activity, was recently reported to induce apoptosis through ROS‐mediated ER stress in NSCLC .…”

Section: Discussionmentioning

confidence: 99%

ω‐hydroxyundec‐9‐enoic acid induces apoptosis by ROS mediated JNK and p38 phosphorylation in breast cancer cell lines

Ahn¹,

Chung

Park³

et al. 2017

J of Cellular Biochemistry

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ω-Hydroxyundec-9-enoic acid (ω-HUA), a plant secondary metabolite, exhibits anti-fungal activity. However, its effect on breast cancer cells is unknown. Here, we investigated the anti-breast cancer activity of ω-HUA and its underlying mechanism. Treatment of human breast cancer cell lines, MDA-MB-231 and MDA-MB-435, with ω-HUA induced apoptotic cell death with increased cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) levels, and p38 and JNK phosphorylation. Inhibition of these mitogen-activated protein kinase (MAPK) pathways using specific inhibitors or siRNA, for p38 and JNK, respectively, blocked the ω-HUA-induced apoptosis in a dose-dependent manner. Moreover, pretreatment of the cells with antioxidant N-acetyl cysteine (NAC) inhibited ω-HUA-induced increased reactive oxygen species (ROS) levels, cleaved caspase-3 and cleaved PARP, and phosphorylated JNK, phosphorylated p38, and increased cell viability and colony-forming ability. MDA-MB-231 xenograft model showed that the ω-HUA-treated group exhibited greater tumor regression and significantly reduced tumor weight compared to that exhibited by the vehicle-administered group. Collectively, ω-HUA-induced intracellular ROS generation induced breast cancer cell apoptosis through JNK and p38 signaling pathway activation, resulting in tumor regression. The results suggested that ω-HUA is an effective supplement for inhibiting human breast cancer growth. K E Y W O R D Santi-cancer effect, apoptosis, JNK pathway, p38 pathway, ROS, ω-Hydroxyundec-9-enoic acid | INTRODUCTIONBreast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related deaths among women. 1The known risk factors include not only older age and family history, but also obesity, excessive drinking, and ionizing radiation; it is generally more aggressive than after menopause.1-3 Compared to the 5-year survival rate of >80% in England and the United States, that in the other countries remains low. 4 Breast cancer can be treated by surgery, radiation therapy, chemotherapy, hormonal therapy, targeted therapy, and drugs, such as tamoxifen and raloxifene. 5-9The intake of dietary fats has long been associated with the prevention and treatment of chronic diseases, such as cancer. Marine resource-derived polyunsaturated fatty acids 998 |

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Section: Discussionmentioning

confidence: 99%

ω‐hydroxyundec‐9‐enoic acid induces apoptosis by ROS mediated JNK and p38 phosphorylation in breast cancer cell lines

Ahn¹,

Chung

Park³

et al. 2017

J of Cellular Biochemistry

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“…In 1998, Hawkins et al27 reported that apoptotic death of human Mia-PaCa-2 pancreatic cancer cells induced by PUFAs varies with double bond number and involves an oxidative mechanism. They found correlations between the number of fatty acid double bonds and the proportion of apoptotic cells.…”

Section: Effect Of Docosahexaenoic Acid On Pancreatic Carcinogenesismentioning

confidence: 99%

Anti-cancer Mechanism of Docosahexaenoic Acid in Pancreatic Carcinogenesis: A Mini-review

Park

Kim

2017

J Cancer Prev

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Pancreatic cancer is a highly aggressive malignant tumor of the digestive system and radical resection, which is available to very few patients, might be the only possibility for cure. Since therapeutic choices are limited at the advanced stage, prevention is more important for reducing incidence in high-risk individuals with family history of pancreatic cancer. Epidemiological studies have shown that a high consumption of fish oil or ω3-polyunsaturated fatty acids reduces the risk of pancreatic cancers. Dietary fish oil supplementation has shown to suppress pancreatic cancer development in animal models. Previous experimental studies revealed that several hallmarks of cancer involved in the pathogenesis of pancreatic cancer, such as the resistance to apoptosis, hyper-proliferation with abnormal Wnt/β-catenin signaling, expression of pro-angiogenic growth factors, and invasion. Docosahexaenoic acid (DHA) is a ω3-polyunsaturated fatty acid and rich in cold oceanic fish oil. DHA shows anti-cancer activity by inducing oxidative stress and apoptosis, inhibiting Wnt/β-catenin signaling, and decreasing extracellular matrix degradation and expression of pro-angiogenic factors in pancreatic cancer cells. This review will summarize anti-cancer mechanism of DHA in pancreatic carcinogenesis based on the recent studies.

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“…Das (1991) demonstrated that the inhibition of tumour cell proliferation in the presence of ␥-linolenic acid, arachidonic acid and EPA was caused by selective cytotoxicity, and that cell death was blocked by antioxidants, enhanced by pro-oxidants and proportional to the degree of peroxidation induced in the cells. More recent studies have confirmed these findings, extended them to other cell lines and shown that apoptosis plays an important role in the cytotoxicity induced by PUFA (Finstad et al 1998;Hawkins et al 1998;Ramesh & Das, 1998). In the human colorectal adenocarcinoma cell line HT29, incubation with EPA leads first to detachment of the cells from the substratum, followed by apoptosis, which can be enhanced by depletion of intracellular glutathione levels (Latham et al 1998), and blocked with antioxidants and caspase inhibitors (Clarke et al 1999).…”

Section: Polyunsaturated Fatty Acidsmentioning

confidence: 75%

Mechanisms and anticarcinogenic effects of diet-related apoptosis in the intestinal mucosa

Johnson

2001

NRR

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There is now ample epidemiological evidence to show that the wide international variations in the incidence of both adenomatous polyps and colo-rectal cancer are linked to diet, but the mechanisms through which particular dietary constituents influence the onset of neoplasia are poorly understood. The crypt epithelial cells of the human gastrointestinal mucosa are amongst the most rapidly proliferating tissues in the body, and those of the colorectum are particularly vulnerable to neoplasia. Within the crypt, continuous division of basally localized stem cells gives rise to daughter cells that may divide once or twice again, before differentiating and migrating to the mucosal surface. The majority of nascent crypt epithelial cells differentiate, become senescent and are shed into the gut lumen, but a small proportion die by apoptosis soon after cell division. Various lines of evidence suggest that these pathways of programmed cell death provide a protective mechanism against induction of neoplasia by removing genetically damaged stem cells before they can divide further and give rise to precancerous lesions. There is evidence that the short-chain fatty acid butyrate and several different classes of food constituents, including some polyunsaturated fatty acids, flavonoids and glucosinolate breakdown products, can regulate the processes of cell proliferation and death in vitro, and in colorectal crypts in vivo. All three classes of food components suppress the emergence of aberrant crypt foci in animal models of carcinogenesis. The cellular mechanisms underlying these phenomena, and their possible significance for human health, are discussed.

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Apoptotic death of pancreatic cancer cells induced by polyunsaturated fatty acids varies with double bond number and involves an oxidative mechanism

Cited by 128 publications

References 26 publications

ω‐hydroxyundec‐9‐enoic acid induces apoptosis by ROS mediated JNK and p38 phosphorylation in breast cancer cell lines

ω‐hydroxyundec‐9‐enoic acid induces apoptosis by ROS mediated JNK and p38 phosphorylation in breast cancer cell lines

Anti-cancer Mechanism of Docosahexaenoic Acid in Pancreatic Carcinogenesis: A Mini-review

Mechanisms and anticarcinogenic effects of diet-related apoptosis in the intestinal mucosa

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