Submitted Successfully!
Thank you for your contribution! You can also upload a video entry related to this topic through the link below: https://encyclopedia.pub/user/video_add?id=25638
Check Note
2000/2000
Ver. Summary Created by Modification Content Size Created at Operation
1 -- 2246 2022-07-29 03:58:50 |
2 Reference format revised. Meta information modification 2246 2022-07-29 04:37:50 | |
3 Adjust second-level title Meta information modification 2246 2022-07-30 03:14:58 |
Marine Products in Colorectal and Pancreatic Cancers Treatment
Edit
Upload a video

Gastrointestinal cancer refers to malignancy of the accessory organs of digestion, and it includes colorectal cancer (CRC) and pancreatic cancer (PC). Worldwide, CRC is the second most common cancer among women and the third most common among men. PC has a poor prognosis and high mortality, with 5-year relative survival of approximately 11.5%. Conventional chemotherapy treatments for these cancers are limited due to severe side effects and the development of drug resistance. Therefore, there is an urgent need to develop new and safe drugs for effective treatment of PC and CRC. Historically, natural sources—plants in particular—have played a dominant role in traditional medicine used to treat a wide spectrum of diseases. In recent decades, marine natural products (MNPs) have shown great potential as drugs, but drug leads for treating various types of cancer, including CRC and PC, are scarce. To date, marine-based drugs have been used against leukemia, metastatic breast cancer, soft tissue sarcoma, and ovarian cancer.

marine natural products colon cancer pancreatic cancer
Information
View Times: 151
Revisions: 3 times (View History)
Update Date: 30 Jul 2022
Table of Contents

    1. Introduction

    Gastrointestinal cancer refers to malignant of accessory organs of digestion, and it includes colorectal cancer (CRC) and pancreatic cancer (PC). In 2020, 1.9 million new CRC cases and 0.9 million CRC deaths were estimated worldwide [1]. The CRC incidence is higher in developed countries; however, the number of cases is increasing in non-developed countries every year [2]. PC is a malignant tumor that usually occurs as a pancreatic adenocarcinoma. It has a poor prognosis and high mortality, with an estimated 5-year relative survival of 11.5% [3]

    Cancer care usually requires teamwork by doctors in multiple disciplines who combine different types of treatments. Treatment options depend on several factors, including the type and stage of cancer, possible side effects, and overall health. The treatment options for CRC and PC are surgery, radiation therapy, chemotherapy, targeted therapy, and immunotherapy [4]. Only about 20% of people diagnosed with PC are able to access surgery due to late stage diagnosis, at which point the disease has already spread. External beam radiation therapy is the type of therapy used most often to treat PC [5]. Medications are also given individually or as a cocktail as part of the treatment plan [5]. Drugs used in chemotherapy induce severe side effects that greatly affect the life quality of patients, including weakness, hair loss, nausea, vomiting, diarrhea, abdominal cramps, mouth sores, dry mouth, and numbness [6]. Therefore, there is an urgent need to identify new chemical targets and active compounds with higher selective potency or new cellular targets.
    Natural products, which are chemical compounds produced by organisms, have been used for centuries as remedies for various illnesses. Since ancient times, humans have utilized natural products from various sources, such as plants, marine organisms, and microorganisms, for diverse applications. 

    2. Marine Natural Products (MNPs) with the Potential to Treat Cancer

    MNPs are compounds isolated from marine microorganisms and phytoplankton, algae, sponges, mollusks, tunicates, echinoderms, mangroves, and others. Since the 1970s, marine organisms have played an important role in the discovery of novel biologically active compounds, and MNPs have become a source of bioactive secondary metabolites with the potential to treat diseases, including cancer [7][8][9].
    The screening of 3019 compounds from the MNPs library identified that four compounds have potential therapeutic anticancer activity through the mammalian target of the rapamycin pathway (mTOR). mTOR regulates different cellular processes including cell growth and cell proliferation [10]. In addition, marine compounds such as glycosides, alkaloids, saponins, lipids, terpenes, ribose, steroids, xanthones, ethers, lignins, coumarins, carbazoles, azaphilones, nucleosides, polyketides, and quinones have been shown to have high cytotoxic activities against 121 mammalian cancer cell lines including breast, colon, melanoma, lung and pancreatic human tumor cells [11]
    Furthermore, recent studies investigated scalarine, a compound isolated from different marine sponges, and demonstrated that it can reduce the level of the receptor for advanced glycation end products (RAGE) and inhibit autophagy in human pancreatic cell lines (PANC-1 and MIA PaCa-2). RAGE has lately become a chemotherapeutic target for both treatment and chemoprevention. RAGE seems to be a key regulator of the inflammatory, stress, and survival pathways that contribute to PC carcinogenesis, chemotherapy resistance, increased proliferation, and a high risk of metastasis. It has been shown that PC tumors express RAGE, but not the surrounding epithelial tissues [12].
    To date, MNPs from different marine species of sponges, tunicates, mollusks, and cyanobacteria have been approved as anti-cancer marine molecules, including Cytosar-U®, Depocyt®, Halaven®, Fludara®, Arranon®, Yondelis®, Adcetris®, Polivy®, Farydak®, Aplidine®, Zepzelca™, Blenrep™, Aidixi™, TIVDAK™, and PADCEV™ [13][14][15]. These drugs have several side effects including severe ones such as a fast or slow heart rate, difficulty breathing, high blood sugar (hyperglycemia), peripheral neuropathy, neutropenia, leukopenia, hypoesthesia, increased conjugated blood bilirubin, decrease in platelets (thrombocytopenia), low blood cell counts, infusion related reactions, and muscle pain (myalgia). In addition, several MNPs are currently being evaluated in different phases of human clinical trials [16][17]. In addition, recent in vitro, in vivo, and clinical studies have shown several marine compounds such as alkaloids, peptides, terpenoids, poly saccharides, and carotenoids have antitumor effects on CRC [18]. However, many MNPs are toxic and their use was terminated in clinical studies. Therefore, continued efforts in the field of marine drug discovery are expected to reveal more potent bioactive compounds with diverse mechanisms of action.

    3. Mechanisms of Action of MNPs in CRC and PC

    3.1. Induction of Apoptosis through Caspase Activation

    Some MNPs were found to affect CRC and PC cells through caspase activation pathways. Caspases are protease enzymes that have essential roles in programmed cell death (apoptosis) [19]. Caspases-2, -3, -6, -7, -8, -9, and -10 are activated during apoptosis. Caspases-2, -8, -9, and -10 are called apical or upstream caspases, and are responsible for initiating caspase activation cascades. Caspases-3, -6, and -7 are called downstream caspases, and are responsible for the actual destruction of the cell during apoptosis [20]. During activation, apical caspases distribute death signals and activate downstream caspases in a cascade-like manner [21]. Downstream caspases then cause direct cellular structures disintegration, cellular metabolism disruption, cell death, inhibitory proteins inactivation, and additional destructive enzymes activation [22]. For example, marine sponge metabolites ilimaquinone and ethylsmenoquinone were found to activate caspase-3 and induce apoptosis via this pathway [23].
    Many apoptosis-inducing stimuli activate caspases through one of the following three major pathways: (i) the mitochondrial pathway (intrinsic pathway), (ii) the death receptor pathway (extrinsic), and (iii) the cytotoxic T lymphocytes/natural killer cells (CTL/NK)-dependent pathway [20] (Figure 1).
    Figure 1. Three major pathways that induce stimuli that activate the caspase apoptosis pathway: (A) Mitochondrial pathway (intrinsic); (B) Caspase pathway; (C) CTL/NK dependent pathway. Bcl-extra-large (Bcl-xL); Bcl-2-associated X protein (Bax); Bcl-2-antagonist/killer (Bak); Bcl-2 associated agonist of cell death (Bad); Bcl-2 interacting mediator of cell death (Bim); Bcl-2 homology-3 (BH3); BH3-interacting domain death agonist (Bid); Apoptosis protease-activating factor-1 (Apaf-1); Deoxyadenosine triphosphate (dATP); Death-inducing signaling complex (DISC); FAS- associated death domain protein (FADD); TNF receptor 1 (TNFR1); TNF-related apoptosis-inducing ligand receptors (TRAIL); inhibitor of apoptosis protein (IAP); Second mitochondria-derived activator of caspases (SMAC); Cytotoxic T lymphocytes/natural killer cells (CTL/NK).

    3.2. Inhibition of Anti-Apoptotic Factors

    One mechanism of resistance to apoptotic stimuli in cancer cells involves the overexpression of the IAP family of proteins. IAPs include X-linked IAP (XIAP), cellular IAP-1 (cIAP-1), and cIAP-2 [24][25]. These proteins have been shown to prevent apoptosis by binding to caspases, including initiators and effectors, and thereby protecting them from cleavage and activation [25][26].
    Kim et al. reported that the fucoidan extract from brown algae attenuated the levels of XIAP and survivin, which are members of the IAP family [27]. Additionally, Zhang et al. found that libertellenone-H (LH) isolated from Arctic marine fungi inhibits the thioredoxin (TRX) system, which leads to cellular stress and cell death in human PC cell lines [28]. The TRX system is expressed in all living cells and has a variety of biological functions related to cell proliferation and apoptosis. It also is a key part of the antioxidant system that defends against oxidative stress. Moreover, the TRX system plays critical roles in the immune response, virus infection, and cell death by interacting with the thioredoxin interacting protein [29]. The TRX system also helps tumor cells evade apoptosis by directly binding to the apoptosis signal regulating kinase and the tumor suppressor gene phosphatase and tensin homolog (PTEN) [30][31].

    3.3. Interaction of MNPs with Tubulin to Cause Anti-Mitotic Activity

    Microtubules are elements of the cytoskeleton and play important roles in many cellular functions, including intracellular transport, motility, morphogenesis, and cell division [32]. Microtubules are heterodimers composed of α-β subunits that assemble to form the protofilaments of the tube [33]. The polymerization and depolymerization of microtubules are critical processes for cell division machinery. Checchi et al. showed that disrupting these processes with microtubule binding drugs could be a useful tool to inhibit cell proliferation [34].
    Leiodermatolide, a MNP isolated from a deep-water sponge, has a cytotoxic effect on human PC and CRC cells. It induces cell cycle arrest and apoptosis, and it affects the microtubules required for spindle formation and chromosome segregation [35]. Another compound, PM060184, isolated from the marine sponge Lithoplocamia lithistoides is considered to be a tubulin binding agent with potent anti-tumor activity [36].

    3.4. Suppression of Cell Cycle Progression

    The cell cycle is a four-stage process in which the cell increases in size (G1 stage), copies its DNA (S stage), prepares to divide (G2 stage), and undergoes mitosis (M stage). The cell cycle is controlled at three checkpoints. The integrity of the DNA is assessed at the G1, G2, and M checkpoints, and the cell cycle is regulated by a family of enzymes called the cyclin-dependent kinases (CDKs) [37].

    3.5. The Role of NFκB and p53 in Apoptosis

    NFκB is involved in the development of cancer. Wang et al. reported that it is constitutively activated in PC cells but not in normal cells [38]. Nakanishi and Toi found that the constitutive activation of NFκB induces anti-apoptotic genes and inhibits apoptosis [39]. The cytoplasmic factor IkappaB (IκB) binds to NFkB and inhibits its translocation to the nucleus. After translocation to the nucleus, NFkB binds to a specific promotor and regulates the transcription of many genes associated with oncogenesis and tumor progression. Several studies have shown that the inhibition of NFκB results in the induction of apoptosis in cancer cells [40][41][42]. Therefore, the inhibition of NFκB antagonizes the survival of cancer cells and induces apoptosis [39].
    While NFκB is known to inhibit apoptosis, the transcription factor p53, a tumor suppressor gene, is an inducer of apoptosis. p53 plays a regulation or progression role in the cell cycle, apoptosis, and genomic stability through multiple mechanisms, including cell cycle arrest, the activation of DNA repair proteins, and induction of apoptosis [43]. p53 limits cell proliferation by the induction of transient G1 cell cycle arrest or apoptosis. The molecular explanation for the p53 mediated growth arrest response is based on its ability to act as a sequence-specific DNA binding transcription factor. p53 has several downstream target genes, such as p21, Mouse Double Minute 2 homolog (MDM2), Growth Arrest and DNA Damage Inducible Alpha (GADD45), cyclin G, and Bax, whose expression products act as regulators of various aspects of cell growth [44][45]. The activation of p53 negatively regulates the expression and NFκB activity of the RelA (p65) subunit [43].

    3.6. Increased Intracellular ROS Accumulation and Induction of Apoptosis

    Oxygen molecules are a diradicals and are not reactive compared to other molecules. However, incomplete oxygen reduction leads to the formation of more chemically reactive oxygen species (ROS), which include superoxide anion (O2), hydrogen peroxide (H2O2), and hydroxyl radical (radical OH). Due to their strong chemical reactivity, ROS have traditionally been thought to mediate only oxygen toxicity. ROS have been implicated in oxidative stress mediated pathology, as they are considered disruptive agents that can structurally and functionally affect macromolecules such as nucleic acids, proteins, and lipids [46]. Several studies found that the accumulation of ROS decreases mitochondrial membrane potential (MMP) and mitochondria depolarization. The presence of ROS leads to cell cycle arrest at the G2/M phase, followed by the accumulation of DNA damage and induction of apoptosis [47][48]. Other researchers reported that marine extracts from nudibranchs, brown algae, and Arctic fungi trigger the intracellular accumulation of ROS in cancer cells originated from human CRC and PC, leading to apoptosis [28][49][50]. LH, a pimarane diterpenoid isolated from the Arctic marine fungus Eutypella sp. D-1, has effective cytotoxicity against a range of cancer cells and induces ROS accumulation. Further, Zhang et al. showed that LH exerts anti-proliferative activity against four PC cell lines in a dose-dependent manner, with IC50 values of 3.21, 0.67, 2.78, and 5.53 µM in PANC-1, SW1990, AsPC-1, and BxPC-3, respectively, after 48 h of treatment. In contrast, the IC50 value of LH for a normal pancreatic cell lines (HPDE6-C7) is 10.86 µM [28]. The clear difference between the IC50 value of LH between cancer cells and normal cells highlights LH as a potential drug lead.

    4. Conclusions

    MNPs have great potential as new compounds that can assist in the prevention and treatment of cancer, but extensive exploration is needed. Over the past 50 years, many MNPs with beneficial effects on the prevention and treatment of various types of cancer have been reported. For example, cytarabine, eribulin mesylate, brentuximab vedotin, and trabectidine are marine-based drugs used against leukemia, metastatic breast cancer, soft tissue sarcoma, and ovarian cancer [51][52]. MNPs compounds have different activities including the inhibition of the transformation of normal cells into tumor cells, halting tumor cell growth and microtumors development, and inducing apoptosis. A higher consumption of sea food is suggested as a promising strategy to prevent cancer [53][54]. Many marine edible organisms contain lipids enriched by polyunsaturated fatty acids (PUFAs), such as ω-3 fatty acids that have been shown in many experimental studies to suppress most forms of tumor development, including breast, colon, prostate, liver, and pancreatic tumors [55][56][57].

    References

    1. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA. Cancer J. Clin. 2021, 71, 209–249.
    2. Xi, Y.; Xu, P. Global Colorectal Cancer Burden in 2020 and Projections to 2040. Transl. Oncol. 2021, 14, 101174.
    3. NIH National Cancer Institute. Pancreatic Cancer-Cancer Stat Facts. Available online: https://seer.cancer.gov/statfacts/html/pancreas.html (accessed on 13 March 2022).
    4. Cancer.Net. Colorectal Cancer: Types of Treatment. Available online: https://www.cancer.net/cancer-types/colorectal-cancer/types-treatment (accessed on 13 March 2022).
    5. Pancreatic Cancer: Types of Treatment. Available online: https://www.cancer.net/cancer-types/pancreatic-cancer/types-treatment (accessed on 26 April 2022).
    6. Aslam, M.S.; Naveed, S.; Ahmed, A.; Abbas, Z.; Gull, I.; Athar, M.A. Side Effects of Chemotherapy in Cancer Patients and Evaluation of Patients Opinion about Starvation Based Differential Chemotherapy. J. Cancer Ther. 2014, 2014, 817–822.
    7. Blunt, J.W.; Carroll, A.R.; Copp, B.R.; Davis, R.A.; Keyzers, R.A.; Prinsep, M.R. Marine Natural Products. Nat. Prod. Rep. 2018, 35, 8–53.
    8. Blunt, J.W.; Copp, B.R.; Keyzers, R.A.; Munro, M.H.G.; Prinsep, M.R. Marine Natural Products. Nat. Prod. Rep. 2016, 33, 382–431.
    9. Wu, L.; Ye, K.; Jiang, S.; Zhou, G. Marine Power on Cancer: Drugs, Lead Compounds, and Mechanisms. Mar. Drugs 2021, 19, 488.
    10. Parate, S.; Kumar, V.; Lee, G.; Rampogu, S.; Hong, J.C.; Lee, K.W. Marine-Derived Natural Products as ATP-Competitive MTOR Kinase Inhibitors for Cancer Therapeutics. Pharmaceuticals 2021, 14, 282.
    11. Mbaoji, F.N.; Nweze, J.A.; Yang, L.; Huang, Y.; Huang, S.; Onwuka, A.M.; Peter, I.E.; Mbaoji, C.C.; Jiang, M.; Zhang, Y.; et al. Novel Marine Secondary Metabolites Worthy of Development as Anticancer Agents: A Review. Molecules 2021, 26, 5769.
    12. Guzmán, E.A.; Pitts, T.P.; Diaz, M.C.; Wright, A.E. The Marine Natural Product Scalarin Inhibits the Receptor for Advanced Glycation End Products (RAGE) and Autophagy in the PANC-1 and MIA PaCa-2 Pancreatic Cancer Cell Lines. Investig. New Drugs 2019, 37, 262–270.
    13. Wang, E.; Sorolla, M.A.; Krishnan, P.D.G.; Sorolla, A. From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds. Biomolecules 2020, 10, 248.
    14. Dyshlovoy, S.A.; Honecker, F. Marine Compounds and Cancer: Updates 2020. Mar. Drugs 2020, 18, 643.
    15. Wu, A.C.; Jelielek, K.K.; Le, H.Q.; Butt, M.; Newman, D.J.; Glaser, K.B.; Pierce, M.L.; Mayer, A.M. The 2021 Marine Pharmacology and Pharmaceuticals Pipeline. FASEB J. 2022, 36, L7586.
    16. Li, T.; Wang, N.; Zhang, T.; Zhang, B.; Sajeevan, T.P.; Joseph, V.; Armstrong, L.; He, S.; Yan, X.; Benjamin Naman, C. A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors. Mar. Drugs 2019, 17, 493.
    17. Khalifa, S.A.M.; Elias, N.; Farag, M.A.; Chen, L.; Saeed, A.; Hegazy, M.E.F.; Moustafa, M.S.; El-Wahed, A.A.; Al-Mousawi, S.M.; Musharraf, S.G.; et al. Marine Natural Products: A Source of Novel Anticancer Drugs. Mar. Drugs 2019, 17, 491.
    18. Sarabia, F.; Han, N.; Li, J.; Li, X. Natural Marine Products: Anti-Colorectal Cancer In Vitro and In Vivo. Mar. Drugs 2022, 20, 349.
    19. Denicourt, C.; Dowdy, S.F. Targeting Apoptotic Pathways in Cancer Cells. Science 2004, 305, 1411–1413.
    20. Creagh, E.M.; Conroy, H.; Martin, S.J. Caspase-Activation Pathways in Apoptosis and Immunity. Immunol. Rev. 2003, 193, 10–21.
    21. Slee, E.A.; Harte, M.T.; Kluck, R.M.; Wolf, B.B.; Casiano, C.A.; Newmeyer, D.D.; Wang, H.-G.; Reed, J.C.; Nicholson, D.W.; Alnemri, E.S.; et al. Ordering the Cytochrome c–Initiated Caspase Cascade: Hierarchical Activation of Caspases-2,-3,-6,-7,-8, and-10 in a Caspase-9–Dependent Manner. J. Cell Biol. 1999, 144, 281–292.
    22. Adrain, C.; Martin, S. The Mitochondrial Apoptosome: A Killer Unleashed by the Cytochrome Seas. Trends Biochem. Sci. 2001, 26, 390–397.
    23. Lee, H.; Chung, K.; Hwang, I.; Gwak, J.; Park, S.; Ju, B.; Yun, E.; Kim, D.; Chung, Y.; Na, M.; et al. Activation of P53 with Ilimaquinone and Ethylsmenoquinone, Marine Sponge Metabolites, Induces Apoptosis and Autophagy in Colon Cancer Cells. Mar. Drugs 2015, 13, 543–557.
    24. LaCasse, E.C.; Baird, S.; Korneluk, R.G.; MacKenzie, A.E. The Inhibitors of Apoptosis (IAPs) and Their Emerging Role in Cancer. Oncogene 1998, 17, 3247–3259.
    25. Deveraux, Q.L.; Reed, J.C. IAP Family Proteins—Suppressors of Apoptosis. Genes Dev. 1999, 13, 239–252.
    26. Green, D.R. Apoptotic Pathways: Paper Wraps Stone Blunts Scissors. Cell 2000, 102, 1–4.
    27. Kim, E.J.; Park, S.Y.; Lee, J.Y.; Park, J.H.Y. Fucoidan Present in Brown Algae Induces Apoptosis of Human Colon Cancer Cells. BMC Gastroenterol. 2010, 10, 96.
    28. Zhang, W.; Zhu, Y.; Yu, H.; Liu, X.; Jiao, B.; Lu, X. Libertellenone H, a Natural Pimarane Diterpenoid, Inhibits Thioredoxin System and Induces ROS-Mediated Apoptosis in Human Pancreatic Cancer Cells. Molecules 2021, 26, 315.
    29. Lu, J.; Holmgren, A. The Thioredoxin Antioxidant System. Free Radic. Biol. Med. 2014, 66, 75–87.
    30. Meuillet, E.J.; Mahadevan, D.; Berggren, M.; Coon, A.; Powis, G. Thioredoxin-1 Binds to the C2 Domain of PTEN Inhibiting PTEN’s Lipid Phosphatase Activity and Membrane Binding: A Mechanism for the Functional Loss of PTEN’s Tumor Suppressor Activity. Arch. Biochem. Biophys. 2004, 429, 123–133.
    31. Saitoh, M.; Nishitoh, H.; Fujii, M.; Takeda, K.; Tobiume, K.; Sawada, Y.; Kawabata, M.; Miyazono, K.; Ichijo, H. Mammalian Thioredoxin Is a Direct Inhibitor of Apoptosis Signal-Regulating Kinase (ASK) 1. EMBO J. 1998, 17, 2596–2606.
    32. Nogales, E. Structural Insights into Microtubule Function. Annu. Rev. Biochem. 2000, 69, 277–302.
    33. Valiron, O.; Caudron, N.; Job, D. Microtubule Dynamics. Cell. Mol. Life Sci. CMLS 2001, 58, 2069–2084.
    34. Checchi, P.M.; Nettles, J.H.; Zhou, J.; Snyder, J.P.; Joshi, H.C. Microtubule-Interacting Drugs for Cancer Treatment. Rends Pharmacol. Sci. 2003, 24, 361–365.
    35. Guzman, E.A.; Xu, Q.; Pitts, T.P.; Mitsuhashi, K.O.; Baker, C.; Linley, P.A.; Oestreicher, J.; Tendyke, K.; Winder, P.L.; Suh, E.M.; et al. Leiodermatolide, a Novel Marine Natural Product, Has Potent Cytotoxic and Antimitotic Activity against Cancer Cells, Appears to Affect Microtubule Dynamics, and Exhibits. Int. J. Cancer 2016, 139, 2116–2126.
    36. Martínez-Díez, M.; Guillén-Navarro, M.; Pera, B.; Bouchet, B.; Martínez-Leal, J.; Barasoain, I.; Cuevas, C.; Andreu, J.; García-Fernández, L.; Díaz, J.; et al. PM060184, a New Tubulin Binding Agent with Potent Antitumor Activity Including P-Glycoprotein over-Expressing Tumors. Biochem. Pharmacol. 2014, 88, 291–302.
    37. Lim, S.; Kaldis, P. Cdks, Cyclins and CKIs: Roles beyond Cell Cycle Regulation. Development 2013, 140, 3079–3093.
    38. Wang, W.; Abbruzzese, J.L.; Evans, D.B.; Larry, L.; Cleary, K.R.; Chiao, P.J. The Nuclear Factor-ΚB RelA Transcription Factor Is Constitutively Activated in Human Pancreatic Adenocarcinoma Cells. Clin. Cancer Res. 1999, 5, 119–127.
    39. Nakanishi, C.; Toi, M. Nuclear Factor-ΚB Inhibitors as Sensitizers to Anticancer Drugs. Nat. Rev. Cancer 2005, 5, 297–309.
    40. Arlt, A.; Vorndamm, J.; Breitenbroich, M.; FoÈlsch, U.; Kalthoff, H.; Schmidt, W.E.; SchaÈfer, H. Inhibition of NF-ΚB Sensitizes Human Pancreatic Carcinoma Cells to Apoptosis Induced by Etoposide (VP16) or Doxorubicin. Oncogene 2001, 20, 859–868.
    41. Guo, J.; Verma, U.N.; Gaynor, R.B.; Frenkel, E.P.; Becerra, C.R. Enhanced Chemosensitivity to Irinotecan by RNA Interference-Mediated down-Regulation of the Nuclear Factor-ΚB P65 Subunit. Clin. Cancer Res. 2004, 10, 3333–3341.
    42. Mabuchi, S.; Ohmichi, M.; Nishio, Y.; Hayasaka, T.; Kimura, A.; Ohta, T.; Saito, M.; Kawagoe, J.; Takahashi, K.; Yada-Hashimoto, N.; et al. Inhibition of NFκB Increases the Efficacy of Cisplatin in In Vitro and In Vivo Ovarian Cancer Models. J. Biol. Chem. 2004, 279, 23477–23485.
    43. Delma, C.R.; Thirugnanasambandan, S.; Srinivasan, G.P.; Raviprakash, N.; Manna, S.K.; Natarajan, M.; Aravindan, N. Fucoidan from Marine Brown Algae Attenuates Pancreatic Cancer Progression by Regulating P53–NFκB Crosstalk. Phytochemistry 2019, 167, 112078.
    44. Ko, L.J.; Prives, C. P53: Puzzle and Paradigm. Genes Dev. 1996, 10, 1054–1072.
    45. Levine, A.J. P53, the Cellular Gatekeeper for Growth and Division. Cell 1997, 88, 323–331.
    46. Cross, C.E.; Halliwell, B.; Borish, E.T.; Pryor, W.A.; Ames, B.N.; Saul, R.L.; McCORD, J.M.; Harman, D. Oxygen Radicals and Human Disease. Ann. Intern. Med. 1987, 107, 526–545.
    47. Kim, A.; Ha, J.; Kim, J.; Cho, Y.; Ahn, J.; Cheon, C.; Kim, S.H.; Ko, S.G.; Kim, B. Natural Products for Pancreatic Cancer Treatment: From Traditional Medicine to Modern Drug Discovery. Nutrients 2021, 13, 3801.
    48. Tripathi, S.K.; Biswal, B.K. Pterospermum acerifolium (L.) Wild Bark Extract Induces Anticarcinogenic Effect in Human Cancer Cells through Mitochondrial-Mediated ROS Generation. Mol. Biol. Rep. 2018, 45, 2283–2294.
    49. Ruiz-Torres, V.; Rodríguez-Pérez, C.; Herranz-López, M.; Martín-García, B.; Gómez-Caravaca, A.-M.; Arráez-Román, D.; Segura-Carretero, A.; Barrajón-Catalán, E.; Micol, V. Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment. Biomolecules 2019, 9, 771.
    50. Xu, J.W.; Yan, Y.; Wang, L.; Wu, D.; Nai, K.Y.; Shi, H.C.; Li, F. Marine Bioactive Compound Dieckol Induces Apoptosis and Inhibits the Growth of Human Pancreatic Cancer Cells PANC-1. J. Biochem. Mol. Toxicol. 2021, 35, e22648.
    51. Dyshlovoy, S.A.; Honecker, F. Marine Compounds and Cancer: 2017 Updates. Mar. Drugs 2018, 16, 41.
    52. DrugBank Online|Database for Drug and Drug Target Info. Available online: https://go.drugbank.com/ (accessed on 28 April 2022).
    53. Stonik, V.A.; Fedorov, S.N. Marine Low Molecular Weight Natural Products as Potential Cancer Preventive Compounds. Mar. Drugs 2014, 12, 636–671.
    54. Dyshlovoy, S.A. Recent Updates on Marine Cancer-Preventive Compounds. Mar. Drugs 2021, 19, 558.
    55. Song, M.; Ou, F.-S.; Zemla, T.J.; Hull, M.A.; Shi, Q.; Limburg, P.J.; Alberts, S.R.; Sinicrope, F.A.; Giovannucci, E.L.; Van Blarigan, E.L.; et al. Marine Omega-3 Fatty Acid Intake and Survival of Stage III Colon Cancer According to Tumor Molecular Markers in NCCTG Phase III Trial N0147 (Alliance). Wiley Online Libr. 2019, 145, 380–389.
    56. Candela, C.G.; López, L.B.; Kohen, V.L. Importance of a Balanced Omega 6/Omega 3 Ratio for the Maintenance of Health. Nutritional Recommendations. Nutr. Hosp. 2011, 26, 323–329.
    57. Wendel, M.; Axel, R. Heller Anticancer Actions of Omega-3 Fatty Acids-Current State and Future Perspectives. Anti-Cancer Agents Med. Chem. 2009, 9, 457–470.
    More
    Information
    Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : ,
    View Times: 151
    Revisions: 3 times (View History)
    Update Date: 30 Jul 2022
    Table of Contents
      1000/1000

      Confirm

      Are you sure you want to delete?

      Video Upload Options

      Do you have a full video?
      Cite
      If you have any further questions, please contact Encyclopedia Editorial Office.
      Amer, N.F.; Knaan, T.L. Marine Products in Colorectal and Pancreatic Cancers Treatment. Encyclopedia. Available online: https://encyclopedia.pub/entry/25638 (accessed on 07 February 2023).
      Amer NF, Knaan TL. Marine Products in Colorectal and Pancreatic Cancers Treatment. Encyclopedia. Available at: https://encyclopedia.pub/entry/25638. Accessed February 07, 2023.
      Amer, Nasrin Fares, Tal Luzzatto Knaan. "Marine Products in Colorectal and Pancreatic Cancers Treatment," Encyclopedia, https://encyclopedia.pub/entry/25638 (accessed February 07, 2023).
      Amer, N.F., & Knaan, T.L. (2022, July 29). Marine Products in Colorectal and Pancreatic Cancers Treatment. In Encyclopedia. https://encyclopedia.pub/entry/25638
      Amer, Nasrin Fares and Tal Luzzatto Knaan. ''Marine Products in Colorectal and Pancreatic Cancers Treatment.'' Encyclopedia. Web. 29 July, 2022.
      Top
      Feedback