Inhaled Indomethacin-Loaded Liposomes as Potential Therapeutics against Non-Small Cell Lung Cancer (NSCLC).
COX-2 inhibition
NSCLC
caspase induction
indomethacin
liposomes
Journal
Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
23
06
2022
accepted:
06
09
2022
pubmed:
16
9
2022
medline:
8
11
2022
entrez:
15
9
2022
Statut:
ppublish
Résumé
Most lung cancer instances are non-small cell lung cancers (NSCLC). As stated by recent literature, cycloxygenase-2 (COX-2) is upregulated in lung adenocarcinomas. COX-2 relates to enhanced cell proliferation and reduced apoptosis; both of which are essential for an invasive tumor growth and metastasis. Thus, COX-2 inhibition forms an important checkpoint. Drug repurposing and nano drug delivery systems will enable the faster and more efficacious drug development. This study was designed to prepare, characterize, and establish superior effectiveness of indomethacin (IND), (a nonselective COX-2 inhibitor) as liposomes (IND-Lip). IND-Lip were made using thin film hydration method and physicochemical properties were characterized. Cell viability was performed on NSCLC cell lines (A549, H1299 and H460) Clonogenic, spheroidal, caspase and COX-2 assays were then carried out. IND-Lip were found to have optimum physicochemical properties. Based on IC
Identifiants
pubmed: 36109463
doi: 10.1007/s11095-022-03392-x
pii: 10.1007/s11095-022-03392-x
doi:
Substances chimiques
Liposomes
0
Indomethacin
XXE1CET956
Cyclooxygenase 2
EC 1.14.99.1
Caspases
EC 3.4.22.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2801-2815Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016 Jun;5(3):288–300.
pubmed: 27413711
pmcid: 4931124
Arbour KC, Riely GJ. Systemic Therapy for Locally Advanced and Metastatic Non-Small Cell Lung Cancer: A Review. JAMA. 2019 Aug 27;322(8):764–74.
pubmed: 31454018
Lung Cancer Survival Rates | 5-Year Survival Rates for Lung Cancer [Internet]. [cited 2021 Jul 9]. Available from: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html
Lin C, Wong BCK, Chen H, Bian Z, Zhang G, Zhang X, et al. Pulmonary delivery of triptolide-loaded liposomes decorated with anti-carbonic anhydrase IX antibody for lung cancer therapy. Sci Rep. 2017 Apr 20;7(1):1–12.
Lung Cancer 101 | Lungcancer.org [Internet]. [cited 2020 Mar 7]. Available from: https://www.lungcancer.org/find_information/publications/163-lung_cancer_101/271-treatment_side_effects
Kim HS, Youm HR, Lee JS, Min KW, Chung JH, Park CS. Correlation between cyclooxygenase-2 and tumor angiogenesis in non-small cell lung cancer. Lung Cancer. 2003 Nov;42(2):163–70.
pubmed: 14568683
Yoon JM, Lim JJ, Yoo CG, Lee CT, Bang YJ, Han SK, et al. Adenovirus-uteroglobin suppresses COX-2 expression via inhibition of NF-κB activity in lung cancer cells. Lung Cancer. 2005 May 1;48(2):201–9.
pubmed: 15829319
Sobolewski C, Cerella C, Dicato M, Ghibelli L, Diederich M. The Role of Cyclooxygenase-2 in Cell Proliferation and Cell Death in Human Malignancies. Int J Cell Biol [Internet]. 2010 [cited 2020 Oct 7];2010. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841246/
Gulyas M, Mattsson JSM, Lindgren A, Ek L, LambergLundström K, Behndig A, et al. COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer. Acta Oncol. 2018 Feb;57(2):244–50.
pubmed: 29140138
Liu X, Yue P, Zhou Z, Khuri FR, Sun SY. Death Receptor Regulation and Celecoxib-Induced Apoptosis in Human Lung Cancer Cells. JNCI Journal of the National Cancer Institute. 2004 Dec 1;96(23):1769–80.
pubmed: 15572759
Cyclooxygenase-2 Inhibition Induces Apoptosis Signaling via Death Receptors and Mitochondria in Hepatocellular Carcinoma | Cancer Research [Internet]. [cited 2020 Oct 7]. Available from: https://cancerres.aacrjournals.org/content/66/14/7059.long
Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2002 Dec;29(6 Suppl 16):15–8.
pubmed: 12516034
Disorders F on N and NS, Policy B on HS, Medicine I of. Drug Development Challenges [Internet]. Improving and Accelerating Therapeutic Development for Nervous System Disorders: Workshop Summary. National Academies Press (US); 2014 [cited 2020 Mar 7]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK195047/
Xue H, Li J, Xie H, Wang Y. Review of Drug Repositioning Approaches and Resources. Int J Biol Sci. 2018;14(10):1232–44.
pubmed: 30123072
pmcid: 6097480
Sarvepalli S, Parvathaneni V, Gupta V. Inhalation of repurposed drugs: A promising strategy for treatment of pulmonary arterial hypertension (PAH). :6.
Duarte D, Vale N. Combining repurposed drugs to treat colorectal cancer. Drug Discovery Today. 2022 Jan 1;27(1):165–84.
pubmed: 34592446
Froelich A, Osmałek T, Snela A, Kunstman P, Jadach B, Olejniczak M, et al. Novel microemulsion-based gels for topical delivery of indomethacin: Formulation, physicochemical properties and in vitro drug release studies. J Colloid Interface Sci. 2017 Dec;1(507):323–36.
Sakdiset P, Amnuaikit T, Pichayakorn W, Pinsuwan S. Formulation development of ethosomes containing indomethacin for transdermal delivery. Journal of Drug Delivery Science and Technology. 2019 Aug;1(52):760–8.
Guimarães D, Cavaco-Paulo A, Nogueira E. Design of liposomes as drug delivery system for therapeutic applications. Int J Pharm. 2021 May;15(601): 120571.
Forest V, Pourchez J. Nano-delivery to the lung - by inhalation or other routes and why nano when micro is largely sufficient? Adv Drug Deliv Rev. 2022 Apr;1(183): 114173.
Soehngen EC, Godin-Ostro E, Fielder FG, Ginsberg RS, Slusher MA, Weiner AL. Encapsulation of indomethacin in liposomes provides protection against both gastric and intestinal ulceration when orally administered to rats. Arthritis Rheum. 1988;31(3):414–22.
pubmed: 3358802
Gupta V, Gupta N, Shaik IH, Mehvar R, McMurtry IF, Oka M, et al. Liposomal fasudil, a rho-kinase inhibitor, for prolonged pulmonary preferential vasodilation in pulmonary arterial hypertension. J Control Release. 2013 Apr 28;167(2):189–99.
pubmed: 23353807
pmcid: 3632285
Parvathaneni V, Kulkarni NS, Shukla SK, Farrales PT, Kunda NK, Muth A, et al. Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment. Pharmaceutics [Internet]. 2020 Feb 28 [cited 2020 Oct 8];12(3). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150896/
Wang X, Parvathaneni V, Shukla SK, Kulkarni NS, Muth A, Kunda NK, et al. Inhalable resveratrol-cyclodextrin complex loaded biodegradable nanoparticles for enhanced efficacy against non-small cell lung cancer. Int J Biol Macromol. 2020 Dec;1(164):638–50.
Shukla SK, Kulkarni NS, Chan A, Parvathaneni V, Farrales P, Muth A, et al. Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer. Pharmaceutics. 2019 Oct 28;11(11):559.
pmcid: 6920889
D’Souza S. A Review of In Vitro Drug Release Test Methods for Nano-Sized Dosage Forms [Internet]. Vol. 2014, Advances in Pharmaceutics. Hindawi; 2014 [cited 2020 Oct 8]. p. e304757. Available from: https://www.hindawi.com/journals/ap/2014/304757/
Hua S. Comparison of in vitro dialysis release methods of loperamide-encapsulated liposomal gel for topical drug delivery. Int J Nanomedicine. 2014 Jan;30(9):735–44.
Reagents: Buffer Solutions [Internet]. [cited 2019 Nov 22]. Available from: http://www.uspbpep.com/usp29/v29240/usp29nf24s0_ris1s119.html
Stocke NA, Meenach SA, Arnold SM, Mansour HM, Zach Hilt J. Formulation and Characterization of Inhalable Magnetic Nanocomposite Microparticles (MnMs) for Targeted Pulmonary Delivery via Spray Drying. Int J Pharm. 2015;479(2):320–8.
pubmed: 25542988
Price DN, Stromberg LR, Kunda NK, Muttil P. In Vivo Pulmonary Delivery and Magnetic-Targeting of Dry Powder Nano-in-Microparticles. Mol Pharm. 2017 Dec 4;14(12):4741–50.
pubmed: 29068693
pmcid: 5717619
Vaidya B, Kulkarni NS, Shukla SK, Parvathaneni V, Chauhan G, Damon JK, et al. Development of inhalable quinacrine loaded bovine serum albumin modified cationic nanoparticles: Repurposing quinacrine for lung cancer therapeutics. Int J Pharm. 2020 Mar;15(577): 118995.
Rivolta I, Panariti A, Lettiero B, Sesana S, Gasco P, Gasco MR, et al. Cellular uptake of coumarin-6 as a model drug loaded in solid lipid nanoparticles. J Physiol Pharmacol. 2011 Feb;62(1):45–53.
pubmed: 21451209
Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ, et al. Cell Viability Assays. In: Markossian S, Sittampalam GS, Grossman A, Brimacombe K, Arkin M, Auld D, et al., editors. Assay Guidance Manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2004 [cited 2020 Oct 8]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK144065/
Franken NAP, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc. 2006 Dec;1(5):2315–9.
pubmed: 17406473
Fennema E, Rivron N, Rouwkema J, van Blitterswijk C, de Boer J. Spheroid culture as a tool for creating 3D complex tissues. Trends Biotechnol. 2013 Feb;31(2):108–15.
pubmed: 23336996
Zanoni M, Piccinini F, Arienti C, Zamagni A, Santi S, Polico R, et al. 3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained. Sci Rep. 2016 Jan 11;6(1):19103.
pubmed: 26752500
pmcid: 4707510
Lukowski JK, Weaver EM, Hummon AB. Analyzing Liposomal Drug Delivery Systems in Three-Dimensional Cell Culture Models Using MALDI Imaging Mass Spectrometry. Anal Chem. 2017 Aug 15;89(16):8453–8.
pubmed: 28731323
pmcid: 5567673
Tumor-Spheroid-Formation-Assay [Internet]. Sigma-Aldrich. [cited 2020 Oct 8]. Available from: https://www.sigmaaldrich.com/technical-documents/protocols/biology/cell-culture/tumor-spheroid-formation-assay.html
Parvathaneni V, Kulkarni NS, Chauhan G, Shukla SK, Elbatanony R, Patel B, et al. Development of pharmaceutically scalable inhaled anti-cancer nanotherapy – Repurposing amodiaquine for non-small cell lung cancer (NSCLC). Mater Sci Eng, C. 2020 Oct;1(115): 111139.
Guyon J, Andrique L, Pujol N, Røsland GV, Recher G, Bikfalvi A, et al. A 3D Spheroid Model for Glioblastoma. J Vis Exp. 2020 Apr 9;(158).
Norouzi S, Norouzi M, Amini M, Amanzadeh A, Nabiuni M, Irian S, et al. Two COX-2 inhibitors induce apoptosis in human erythroleukemia K562cells by modulating NF-κB and FHC pathways. Daru [Internet]. 2016 Jan 7 [cited 2020 Oct 8];24. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704250/
Liu P, Rong X, Laru J, van Veen B, Kiesvaara J, Hirvonen J, et al. Nanosuspensions of poorly soluble drugs: Preparation and development by wet milling. Int J Pharm. 2011 Jun 15;411(1):215–22.
pubmed: 21458552
Pan X, Julian T, Augsburger L. Quantitative measurement of indomethacin crystallinity in indomethacin-silica gel binary system using differential scanning calorimetry and X-ray powder diffractometry. AAPS PharmSciTech. 2006 Mar;7(1):E72–8.
pubmed: 28290026
pmcid: 2750718
Resources - Dissolution Methods Database: | USP [Internet]. [cited 2020 Dec 20]. Available from: https://www.usp.org/resources/dissolution-methods-database
Mathematical models of drug release. In: Strategies to Modify the Drug Release from Pharmaceutical Systems [Internet]. Elsevier; 2015 [cited 2020 Feb 22]. p. 63–86. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780081000922000059
Lee JH, Yeo Y. Controlled Drug Release from Pharmaceutical Nanocarriers. Chem Eng Sci. 2015;125:75–84.
pubmed: 25684779
Phan HT, Haes AJ. What Does Nanoparticle Stability Mean? J Phys Chem C Nanomater Interfaces. 2019;123(27):16495–507.
pubmed: 31844485
pmcid: 6913534
Parvathaneni V, Goyal M, Kulkarni NS, Shukla SK, Gupta V. Nanotechnology Based Repositioning of an Anti-Viral Drug for Non-Small Cell Lung Cancer (NSCLC). Pharm Res. 2020 Jun 8;37(7):123.
pubmed: 32514688
Rau JL. The Inhalation of Drugs: Advantages and Problems. Respir Care. 2005;50(3):16.
Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol. 2003;56(6):588–99.
pubmed: 14616418
pmcid: 1884307
Carvalho TC, Peters JI, Williams RO. Influence of particle size on regional lung deposition – What evidence is there? Int J Pharm. 2011 Mar 15;406(1):1–10.
pubmed: 21232585
Johal B, Howald M, Fischer M, Marshall J, Venthoye G. Fine Particle Profile of Fluticasone Propionate/Formoterol Fumarate Versus Other Combination Products: the DIFFUSE Study. Comb Prod Ther. 2013 Dec 1;3(1):39–51.
Pretor S, Bartels J, Lorenz T, Dahl K, Finke JH, Peterat G, et al. Cellular Uptake of Coumarin-6 under Microfluidic Conditions into HCE-T Cells from Nanoscale Formulations. Mol Pharmaceutics. 2015 Jan 5;12(1):34–45.
Ibrahim WN, Rosli LMBM, Doolaanea AA. <p>Formulation, Cellular Uptake and Cytotoxicity of Thymoquinone-Loaded PLGA Nanoparticles in Malignant Melanoma Cancer Cells</p>. IJN. 2020 Oct;20(15):8059–74.
Shukla SK, Kulkarni NS, Farrales P, Kanabar DD, Parvathaneni V, Kunda NK, et al. Sorafenib Loaded Inhalable Polymeric Nanocarriers against Non-Small Cell Lung Cancer. Pharm Res. 2020 Mar 12;37(3):67.
pubmed: 32166411
Tahara K, Yamamoto H, Kawashima Y. Cellular uptake mechanisms and intracellular distributions of polysorbate 80-modified poly (d, l-lactide-co-glycolide) nanospheres for gene delivery. Eur J Pharm Biopharm. 2010 Jun 1;75(2):218–24.
pubmed: 20332026
Muntoni E, Marini E, Ferraris C, Garelli S, Capucchio MT, Colombino E, et al. Intranasal lipid nanocarriers: Uptake studies with fluorescently labeled formulations. Colloids Surf, B. 2022 Jun;1(214): 112470.
Jagwani S, Jalalpure S, Dhamecha D, Jadhav K, Bohara R. Pharmacokinetic and Pharmacodynamic Evaluation of Resveratrol Loaded Cationic Liposomes for Targeting Hepatocellular Carcinoma. ACS Biomater Sci Eng. 2020 Sep 14;6(9):4969–84.
pubmed: 33455290
Mayer LD, Tardi P, Louie AC. CPX-351: a nanoscale liposomal co-formulation of daunorubicin and cytarabine with unique biodistribution and tumor cell uptake properties. Int J Nanomedicine. 2019 May;23(14):3819–30.
Fröhlich E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine. 2012;7:5577–91.
pubmed: 23144561
pmcid: 3493258
Padhi S, Kapoor R, Verma D, Panda AK, Iqbal Z. Formulation and optimization of topotecan nanoparticles: In vitro characterization, cytotoxicity, cellular uptake and pharmacokinetic outcomes. J Photochem Photobiol, B. 2018 Jun;1(183):222–32.
Smits EAW, Soetekouw JA, Pieters EHE, Smits CJP, de Wijs-Rot N, Vromans H. The availability of drug by liposomal drug delivery. Invest New Drugs. 2019 Oct 1;37(5):890–901.
pubmed: 30547315
Gomes ER, Novais MVM, Silva IT, Barros ALB, Leite EA, Munkert J, et al. Long-circulating and fusogenic liposomes loaded with a glucoevatromonoside derivative induce potent antitumor response. Biomed Pharmacother. 2018 Dec;1(108):1152–61.
Vaidya B, Parvathaneni V, Kulkarni NS, Shukla SK, Damon JK, Sarode A, et al. Cyclodextrin modified erlotinib loaded PLGA nanoparticles for improved therapeutic efficacy against non-small cell lung cancer. Int J Biol Macromol. 2019 Feb;1(122):338–47.
Caspase 3, the executioner of apoptosis [Internet]. Novus Biologicals. 2015 [cited 2020 Sep 28]. Available from: https://www.novusbio.com/antibody-news/antibodies/caspase-3-the-executioner-of-apoptosis
Fujii Y, Matsura T, Kai M, Matsui H, Kawasaki H, Yamada K. Mitochondrial cytochrome c release and caspase-3-like protease activation during indomethacin-induced apoptosis in rat gastric mucosal cells. Proc Soc Exp Biol Med. 2000 Jun;224(2):102–8.
pubmed: 10806417
de Groot DJA, Timmer T, Spierings DCJ, Le TKP, de Jong S, de Vries EGE. Indomethacin-induced activation of the death receptor-mediated apoptosis pathway circumvents acquired doxorubicin resistance in SCLC cells. Br J Cancer. 2005 Apr;92(8):1459–66.
pubmed: 15812552
pmcid: 2361992
Kim WH, Yeo M, Kim MS, Chun SB, Shin EC, Park JH, et al. Role of caspase-3 in apoptosis of colon cancer cells induced by nonsteroidal anti-inflammatory drugs. Int J Colorectal Dis. 2000 May 3;15(2):105–11.
pubmed: 10855553
Kim HS, Sharma A, Ren WX, Han J, Kim JS. COX-2 Inhibition mediated anti-angiogenic activatable prodrug potentiates cancer therapy in preclinical models. Biomaterials. 2018 Dec;185:63–72.
pubmed: 30223141
Zeng L, Zhen Y, Chen Y, Zou L, Zhang Y, Hu F, et al. Naringin inhibits growth and induces apoptosis by a mechanism dependent on reduced activation of NF-κB/COX-2-caspase-1 pathway in HeLa cervical cancer cells. Int J Oncol. 2014 Nov 1;45(5):1929–36.
pubmed: 25174821
Pereira DM, Valentão P, Andrade PB. Chapter 7 - Lessons from the Sea: Distribution, SAR, and Molecular Mechanisms of Anti-inflammatory Drugs from Marine Organisms. In: Atta-ur-Rahman, editor. Studies in Natural Products Chemistry [Internet]. Elsevier; 2013 [cited 2022 May 13]. p. 205–28. Available from: https://www.sciencedirect.com/science/article/pii/B9780444596031000072
Patel KM, Wright KL, Whittaker P, Chakravarty P, Watson ML, Ward SG. Differential modulation of COX-2 expression in A549 airway epithelial cells by structurally distinct PPAR(gamma) agonists: evidence for disparate functional effects which are independent of NF-(kappa)B and PPAR(gamma). Cell Signal. 2005 Sep;17(9):1098–110.
pubmed: 15993751
Indomethacin: MedlinePlus Drug Information [Internet]. [cited 2020 Sep 29]. Available from: https://medlineplus.gov/druginfo/meds/a681027.html
Munjal A, Allam AE. Indomethacin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 [cited 2020 Sep 29]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK555936/
Petkova DK, Clelland C, Ronan J, Pang L, Coulson JM, Lewis S, et al. Overexpression of cyclooxygenase-2 in non-small cell lung cancer. Respir Med. 2004 Feb 1;98(2):164–72.
pubmed: 14971881
Crommelin DJA, Fransen GJ, Salemink PJM. Stability of Liposomes on Storage. In: Gregoriadis G, Senior J, Poste G, editors. Targeting of Drugs With Synthetic Systems [Internet]. Boston, MA: Springer US; 1986 [cited 2020 Sep 30]. p. 277–87. (NATO ASI Series). Available from: https://doi.org/10.1007/978-1-4684-5185-6_20
Critical Parameters for Particle-Based Pulmonary Delivery of Chemotherapeutics | Journal of Aerosol Medicine and Pulmonary Drug Delivery [Internet]. [cited 2020 Nov 21]. Available from: https://doi.org/10.1089/jamp.2017.1382
Deshpande PP, Biswas S, Torchilin VP. Current trends in the use of liposomes for tumor targeting. Nanomedicine (Lond) [Internet]. 2013 Sep [cited 2020 Oct 1];8(9). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842602/
Haley B, Frenkel E. Nanoparticles for drug delivery in cancer treatment. Urologic Oncology: Seminars and Original Investigations. 2008 Jan;26(1):57–64.
pubmed: 18190833
Kimlin LC, Casagrande G, Virador VM. In vitro three-dimensional (3D) models in cancer research: An update. Mol Carcinog. 2013 Mar;52(3):167–82.
pubmed: 22162252
Fu SL, Wu YL, Zhang YP, Qiao MM, Chen Y. Anti-cancer effects of COX-2 inhibitors and their correlation with angiogenesis and invasion in gastric cancer. World J Gastroenterol. 2004 Jul 1;10(13):1971–4.
pubmed: 15222049
pmcid: 4572243
Zhou XM, Wong BCY, Fan XM, Zhang HB, Lin MCM, Kung HF, et al. Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak. Carcinogenesis. 2001 Sep 1;22(9):1393–7.
pubmed: 11532860
Lin C, Crawford DR, Lin S, Hwang J, Sebuyira A, Meng R, et al. Inducible COX-2-dependent apoptosis in human ovarian cancer cells. Carcinogenesis. 2011 Jan 1;32(1):19–26.
pubmed: 21187340
Kassab SE. Indomethacin from Anti-Inflammatory to Anticancer Agent [Internet]. Medicinal Chemistry. IntechOpen; 2018 [cited 2022 Jul 19]. Available from: https://www.intechopen.com/chapters/undefined/state.item.id
Seetha A, Devaraj H, Sudhandiran G. Indomethacin and juglone inhibit inflammatory molecules to induce apoptosis in colon cancer cells. J Biochem Mol Toxicol. 2020 Feb;34(2): e22433.
pubmed: 31916655
Wang HM, Zhang GY. Indomethacin suppresses growth of colon cancer via inhibition of angiogenesis in vivo. World J Gastroenterol. 2005 Jan 21;11(3):340–3.
pubmed: 15637740
pmcid: 4205333
Tse AKW, Cao HH, Cheng CY, Kwan HY, Yu H, Fong WF, et al. Indomethacin Sensitizes TRAIL-Resistant Melanoma Cells to TRAIL-Induced Apoptosis through ROS-Mediated Upregulation of Death Receptor 5 and Downregulation of Survivin. J Investig Dermatol. 2014 May 1;134(5):1397–407.
pubmed: 24213373