Background: Pancreatic ductal adenocarcinoma (PDAC) is a notoriously aggressive type of cancer with a high metastasis rate. It is conventionally treated by surgical resection and neoadjuvant chemotherapy. However, continuous chemotherapy leads to relapse in most PDAC patients due to chemical resistance. Therefore, novel anticancer agents need to be identified and developed. The antitumor activities of laminarin extracted from brown algae against hepatocarcinoma, lung, and colon cancer have been established. However, its effects on pancreatic cancer have remained obscure. Purpose: Our study identified the anticancer effects of laminarin on pancreatic cancer cells and tried to explain its intracellular mechanisms. Methods: We assessed the cell viability of PANC-1 and MIA PaCa-2 cells using MTT assay. Hanging drop method was used for the spheroid formation. Flow cytometry was conducted to evaluate the several intracellular alterations including apoptosis, ROS production, mitochondrial membrane potential (MMP), and calcium concentration induced by laminarin. An invasion test was performed to assess the inhibitory effect of laminarin on cell migration and the invasive genes were evaluated by RT-qPCR. Signaling pathway related with anticancer effects of laminarin was analyzed by western blot. Results: We report that inhibiting laminarin increased the proliferation and viability of the representative pancreatic cancer cell lines, MIA PaCa-2 and PANC-1. Laminarin triggered apoptosis and mitochondrial impairment as evidenced by depolarized mitochondrial membranes, disrupted calcium, and suppressed cell migration caused by reactive oxygen species production and related intracellular signaling pathways. Moreover, laminarin showed synergistic effects when combined with 5-FU, a standard anticancer agent for PDAC. Conclusion: The present study is the first to report that laminarin exerts anticancer effect through ROS production in pancreatic cancer cells. Laminarin shows potential to serve as a new anticancer agent for treating PDAC.
Recent studies have identified obesity as one of the world’s most serious chronic disorders. Adipogenesis, in which preadipocytes are differentiated into mature adipocytes, has a decisive role in establishing the number of adipocytes and determining the lipid storage capacity of adipose tissue and fat mass in adults. Fat accumulation in obesity is implicated with elevated oxidative stress in adipocytes induced by reactive oxygen species (ROS). Adipogenesis regulation by inhibiting adipogenic differentiation and ROS production has been selected as the strategy to treat obesity. The conventional anti-obesity drugs allowed by the U.S. Food and Drug Administration have severe adverse effects. Therefore, various natural products have been developed as a solution for obesity, suppressing adipogenic differentiation. Fraxetin is a major component extracted from the stem barks of Fraxinus rhynchophylla, with various bioactivities, including anti-inflammatory, anticancer, antioxidant, and antibacterial functions. However, the effect of fraxetin on adipogenesis is still not clearly understood. We studied the pharmacological functions of fraxetin in suppressing lipid accumulation and its underlying molecular mechanisms involving 3T3-L1 preadipocytes. Moreover, increased ROS production induced by a mixture of insulin, dexamethasone, and 3-isobutylmethylxanthine (MDI) in 3T3-L1 was attenuated by fraxetin during adipogenesis. These effects were regulated by mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, our findings imply that fraxetin possesses inhibitory roles in adipogenesis and can be a potential anti-obesity drug.
Pancreatic ductal adenocarcinoma (PDAC) has naturally aggressive characteristics including postoperative recurrence, resistance to conventional treatment, and metastasis. Surgical resection with chemotherapeutic agents has been conducted as the major treatment for PDAC. However, surgical treatment is ineffective in the case of advanced cancer, and conventional adjuvant chemotherapy, including gemcitabine and 5-fluorouracil, show low effectiveness due to the high drug resistance of PDAC to this type of treatment. Therefore, the development of innovative therapeutic drugs is crucial to solving the present limitation of conventional drugs. Glucotropaeolin (GT) is a glucosinolate that can be isolated from the Brassicaceae family. GT has exhibited a growth-inhibitory effect against liver and colon cancer cells; however, there is no study regarding the anticancer effect of GT on PDAC. In our study, we determined the antiproliferative effect of GT in PANC-1 and MIA PaCa-2, representative of PDAC. We revealed the intracellular mechanisms underlying the anticancer effect of GT with respect to cell viability, reactive oxygen species (ROS) accumulation, alteration of mitochondrial membrane potential (MMP), calcium dysregulation, cell migration, and the induction of apoptosis. Moreover, GT regulated the signaling pathways related to anticancer in PDAC cells. Finally, the silencing of the forkhead box protein M, a key factor regulating PDAC progression, contributes to the anticancer property of GT in terms of the induction of apoptosis and cell migration. Therefore, GT may be a potential therapeutic drug against PDAC.
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