Skip to main content
Erschienen in: Medical Oncology 2/2022

01.02.2022 | Original Paper

Mefenamic acid as a promising therapeutic medicine against colon cancer in tumor-bearing mice

verfasst von: Reza Seyyedi, Fereshteh Talebpour Amiri, Soghra Farzipour, Ehsan Mihandoust, Seyed Jalal Hosseinimehr

Erschienen in: Medical Oncology | Ausgabe 2/2022

Einloggen, um Zugang zu erhalten

Abstract

Although radiotherapy is an effective strategy for cancer treatment, tumor resistance to ionizing radiation (IR) and its toxic effects on normal tissues are limiting its use. The aim of this study is to evaluate the anti-cancer effects of mefenamic acid (MEF), as an approved medicine, and its combination with IR against colon tumor cells in mice. Tumor-bearing mice were received MEF at a dose of 25 mg/kg for 6 successive days. The tumor size was measured. In the second experiment, after MEF treatment, tumor-bearing mice locally received an X-ray at dose 6 Gy. Tumor growth and biochemical, histological, and immunohistological assay (caspase-3) were performed. MEF significantly decreased tumor size in mice in comparison to the control group. IR and/or MEF treatment significantly reduced the tumor volume and inhibited tumor growth by 49%, 55%, and 67% by MEF, IR, and MEF + IR groups as compared with the control group. Administration of MEF in combination with radiation had a synergistic effect on enhanced histopathological changes in tumor tissues. MEF treatment in IR exposure mice showed a significant increase in the immunoreactivity of caspase-3 in the colon tumor tissue. MEF has an anti-tumor effect in colon tumor-bearing mice. MEF in combination with IR increased pathological changes and apoptosis in tumor tissues, suggesting that MEF might be clinically useful in the treatment of colon cancer.

Graphical abstract

Literatur
1.
Zurück zum Zitat Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89–103.PubMedPubMedCentral Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89–103.PubMedPubMedCentral
2.
Zurück zum Zitat Hu T, Li Z, Gao CY, Cho CH. Mechanisms of drug resistance in colon cancer and its therapeutic strategies. World J Gastroenterol. 2016;22(30):6876–89.CrossRef Hu T, Li Z, Gao CY, Cho CH. Mechanisms of drug resistance in colon cancer and its therapeutic strategies. World J Gastroenterol. 2016;22(30):6876–89.CrossRef
3.
Zurück zum Zitat Savjani JK, Mulamkattil S, Variya B, Patel S. Molecular docking, synthesis and biological screening of mefenamic acid derivatives as anti-inflammatory agents. Eur J Pharmacol. 2017;801:28–34.CrossRef Savjani JK, Mulamkattil S, Variya B, Patel S. Molecular docking, synthesis and biological screening of mefenamic acid derivatives as anti-inflammatory agents. Eur J Pharmacol. 2017;801:28–34.CrossRef
4.
Zurück zum Zitat Armagan G, Turunc E, Kanit L, Yalcin A. Neuroprotection by mefenamic acid against D-serine: involvement of oxidative stress, inflammation and apoptosis. Free Radic Res. 2012;46(6):726–39.CrossRef Armagan G, Turunc E, Kanit L, Yalcin A. Neuroprotection by mefenamic acid against D-serine: involvement of oxidative stress, inflammation and apoptosis. Free Radic Res. 2012;46(6):726–39.CrossRef
5.
Zurück zum Zitat Asanuma M, Nishibayashi-Asanuma S, Miyazaki I, Kohno M, Ogawa N. Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals. J Neurochem. 2001;76(6):1895–904.CrossRef Asanuma M, Nishibayashi-Asanuma S, Miyazaki I, Kohno M, Ogawa N. Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals. J Neurochem. 2001;76(6):1895–904.CrossRef
6.
Zurück zum Zitat Hosseinimehr SJ, Nobakht R, Ghasemi A, Pourfallah TA. Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes. Radiat Oncol J. 2015;33(3):256–60.CrossRef Hosseinimehr SJ, Nobakht R, Ghasemi A, Pourfallah TA. Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes. Radiat Oncol J. 2015;33(3):256–60.CrossRef
7.
Zurück zum Zitat Hosseinimehr SJ, Safavi Z, Kangarani Farahani S, Noaparst Z, Ghasemi A, Asgarian-Omran H. The synergistic effect of mefenamic acid with ionizing radiation in colon cancer. J Bioenerg Biomembr. 2019;51(3):249–57.CrossRef Hosseinimehr SJ, Safavi Z, Kangarani Farahani S, Noaparst Z, Ghasemi A, Asgarian-Omran H. The synergistic effect of mefenamic acid with ionizing radiation in colon cancer. J Bioenerg Biomembr. 2019;51(3):249–57.CrossRef
8.
Zurück zum Zitat Euhus DM, Hudd C, Laregina MC, Johnson FE. Tumor measurement in the nude mouse. J Surg Oncol. 1986;31(4):229–34.CrossRef Euhus DM, Hudd C, Laregina MC, Johnson FE. Tumor measurement in the nude mouse. J Surg Oncol. 1986;31(4):229–34.CrossRef
9.
Zurück zum Zitat Tomayko MM, Reynolds CP. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol. 1989;24(3):148–54.CrossRef Tomayko MM, Reynolds CP. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol. 1989;24(3):148–54.CrossRef
10.
Zurück zum Zitat Jeong H, Lee SY, Seo H, Kim BJ. Recombinant Mycobacterium smegmatis delivering a fusion protein of human macrophage migration inhibitory factor (MIF) and IL-7 exerts an anticancer effect by inducing an immune response against MIF in a tumor-bearing mouse model. J Immunother Cancer. 2021;9(8):e003180.CrossRef Jeong H, Lee SY, Seo H, Kim BJ. Recombinant Mycobacterium smegmatis delivering a fusion protein of human macrophage migration inhibitory factor (MIF) and IL-7 exerts an anticancer effect by inducing an immune response against MIF in a tumor-bearing mouse model. J Immunother Cancer. 2021;9(8):e003180.CrossRef
11.
Zurück zum Zitat Sharif M, Najafizadeh P, Asgarpanah J, Mousavi Z. In vivo analgesic and anti-inflammatory effects of the essential oil from Tanacetum balsamita L. Braz J Pharm Sci. 2020;56:e18357.CrossRef Sharif M, Najafizadeh P, Asgarpanah J, Mousavi Z. In vivo analgesic and anti-inflammatory effects of the essential oil from Tanacetum balsamita L. Braz J Pharm Sci. 2020;56:e18357.CrossRef
12.
Zurück zum Zitat Naeimi RA, Amiri FT, Khalatbary AR, Ghasemi A, Zargari M, Ghesemi M, et al. Atorvastatin mitigates testicular injuries induced by ionizing radiation in mice. Reprod Toxicol. 2017;72:115.CrossRef Naeimi RA, Amiri FT, Khalatbary AR, Ghasemi A, Zargari M, Ghesemi M, et al. Atorvastatin mitigates testicular injuries induced by ionizing radiation in mice. Reprod Toxicol. 2017;72:115.CrossRef
13.
Zurück zum Zitat Xu Y, Lei H, Guan R, Gao Z, Li H, Wang L, et al. Studies on the mechanism of testicular dysfunction in the early stage of a streptozotocin induced diabetic rat model. Biochem Biophys Res Commun. 2014;450(1):87–92.CrossRef Xu Y, Lei H, Guan R, Gao Z, Li H, Wang L, et al. Studies on the mechanism of testicular dysfunction in the early stage of a streptozotocin induced diabetic rat model. Biochem Biophys Res Commun. 2014;450(1):87–92.CrossRef
14.
Zurück zum Zitat Ahn D, Lee GJ, Sohn JH, Lee JE. Phase II trial of individualized/dynamic cisplatin regimens for definitive concurrent chemoradiation therapy in patients with head and neck squamous cell carcinoma. Cancer Med. 2020;9(24):9256–65.CrossRef Ahn D, Lee GJ, Sohn JH, Lee JE. Phase II trial of individualized/dynamic cisplatin regimens for definitive concurrent chemoradiation therapy in patients with head and neck squamous cell carcinoma. Cancer Med. 2020;9(24):9256–65.CrossRef
15.
Zurück zum Zitat Horsman MR, Bohm L, Margison GP, Milas L, Rosier JF, Safrany G, et al. Tumor radiosensitizers–current status of development of various approaches: report of an International Atomic Energy Agency meeting. Int J Radiat Oncol Biol Phys. 2006;64(2):551–61.CrossRef Horsman MR, Bohm L, Margison GP, Milas L, Rosier JF, Safrany G, et al. Tumor radiosensitizers–current status of development of various approaches: report of an International Atomic Energy Agency meeting. Int J Radiat Oncol Biol Phys. 2006;64(2):551–61.CrossRef
16.
Zurück zum Zitat Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, et al. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017;28(4):777–83.CrossRef Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, et al. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017;28(4):777–83.CrossRef
17.
Zurück zum Zitat Sigmond J, Honeywell RJ, Postma TJ, Dirven CM, de Lange SM, van der Born K, et al. Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer. Ann Oncol. 2009;20(1):182–7.CrossRef Sigmond J, Honeywell RJ, Postma TJ, Dirven CM, de Lange SM, van der Born K, et al. Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer. Ann Oncol. 2009;20(1):182–7.CrossRef
18.
Zurück zum Zitat Lucas GNC, Leitao ACC, Alencar RL, Xavier RMF, Daher EF, Silva Junior GBD. Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs. J Bras Nefrol. 2019;41(1):124–30.CrossRef Lucas GNC, Leitao ACC, Alencar RL, Xavier RMF, Daher EF, Silva Junior GBD. Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs. J Bras Nefrol. 2019;41(1):124–30.CrossRef
19.
Zurück zum Zitat Prusakiewicz JJ, Duggan KC, Rouzer CA, Marnett LJ. Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid. Biochemistry. 2009;48(31):7353–5.CrossRef Prusakiewicz JJ, Duggan KC, Rouzer CA, Marnett LJ. Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid. Biochemistry. 2009;48(31):7353–5.CrossRef
20.
Zurück zum Zitat Radi ZA, Khan KN. Cardio-renal safety of non-steroidal anti-inflammatory drugs. J Toxicol Sci. 2019;44(6):373–91.CrossRef Radi ZA, Khan KN. Cardio-renal safety of non-steroidal anti-inflammatory drugs. J Toxicol Sci. 2019;44(6):373–91.CrossRef
21.
Zurück zum Zitat Hashemi Goradel N, Najafi M, Salehi E, Farhood B, Mortezaee K. Cyclooxygenase-2 in cancer: a review. J Cell Physiol. 2019;234(5):5683–99.CrossRef Hashemi Goradel N, Najafi M, Salehi E, Farhood B, Mortezaee K. Cyclooxygenase-2 in cancer: a review. J Cell Physiol. 2019;234(5):5683–99.CrossRef
22.
Zurück zum Zitat Salehifar E, Hosseinimehr SJ. The use of cyclooxygenase-2 inhibitors for improvement of efficacy of radiotherapy in cancers. Drug Discov Today. 2016;21(4):654–62.CrossRef Salehifar E, Hosseinimehr SJ. The use of cyclooxygenase-2 inhibitors for improvement of efficacy of radiotherapy in cancers. Drug Discov Today. 2016;21(4):654–62.CrossRef
23.
Zurück zum Zitat Lin EH, Curley SA, Crane CC, Feig B, Skibber J, Delcos M, et al. Retrospective study of capecitabine and celecoxib in metastatic colorectal cancer: potential benefits and COX-2 as the common mediator in pain, toxicities and survival? Am J Clin Oncol. 2006;29(3):232–9.CrossRef Lin EH, Curley SA, Crane CC, Feig B, Skibber J, Delcos M, et al. Retrospective study of capecitabine and celecoxib in metastatic colorectal cancer: potential benefits and COX-2 as the common mediator in pain, toxicities and survival? Am J Clin Oncol. 2006;29(3):232–9.CrossRef
24.
Zurück zum Zitat Shiiba M, Yamagami H, Yamamoto A, Minakawa Y, Okamoto A, Kasamatsu A, et al. Mefenamic acid enhances anticancer drug sensitivity via inhibition of aldo-keto reductase 1C enzyme activity. Oncol Rep. 2017;37(4):2025–32.CrossRef Shiiba M, Yamagami H, Yamamoto A, Minakawa Y, Okamoto A, Kasamatsu A, et al. Mefenamic acid enhances anticancer drug sensitivity via inhibition of aldo-keto reductase 1C enzyme activity. Oncol Rep. 2017;37(4):2025–32.CrossRef
25.
Zurück zum Zitat Woo DH, Han IS, Jung G. Mefenamic acid-induced apoptosis in human liver cancer cell-lines through caspase-3 pathway. Life Sci. 2004;75(20):2439–49.CrossRef Woo DH, Han IS, Jung G. Mefenamic acid-induced apoptosis in human liver cancer cell-lines through caspase-3 pathway. Life Sci. 2004;75(20):2439–49.CrossRef
26.
Zurück zum Zitat August EM, Nguyen T, Malinowski NM, Cysyk RL. Non-steroidal anti-inflammatory drugs and tumor progression: inhibition of fibroblast hyaluronic acid production by indomethacin and mefenamic acid. Cancer Lett. 1994;82(1):49–54.CrossRef August EM, Nguyen T, Malinowski NM, Cysyk RL. Non-steroidal anti-inflammatory drugs and tumor progression: inhibition of fibroblast hyaluronic acid production by indomethacin and mefenamic acid. Cancer Lett. 1994;82(1):49–54.CrossRef
27.
Zurück zum Zitat Shati AA, Alkahtani MA, Alfaifi MY, Elbehairi SEI, Elsaid FG, Prasanna R, et al. Secondary metabolites of saussurea costus leaf extract induce apoptosis in breast, liver, and colon cancer cells by caspase-3-dependent intrinsic pathway. BioMed Res Int. 2020;2020:1608942.CrossRef Shati AA, Alkahtani MA, Alfaifi MY, Elbehairi SEI, Elsaid FG, Prasanna R, et al. Secondary metabolites of saussurea costus leaf extract induce apoptosis in breast, liver, and colon cancer cells by caspase-3-dependent intrinsic pathway. BioMed Res Int. 2020;2020:1608942.CrossRef
28.
Zurück zum Zitat Zhou P, Wang C, Hu Z, Chen W, Qi W, Li A. Genistein induces apoptosis of colon cancer cells by reversal of epithelial-to-mesenchymal via a Notch1/NF-kappaB/slug/E-cadherin pathway. BMC Cancer. 2017;17(1):813.CrossRef Zhou P, Wang C, Hu Z, Chen W, Qi W, Li A. Genistein induces apoptosis of colon cancer cells by reversal of epithelial-to-mesenchymal via a Notch1/NF-kappaB/slug/E-cadherin pathway. BMC Cancer. 2017;17(1):813.CrossRef
29.
Zurück zum Zitat Foxtrot CG. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol. 2012;13(11):1152–60.CrossRef Foxtrot CG. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol. 2012;13(11):1152–60.CrossRef
30.
Zurück zum Zitat Huang CM, Huang MY, Ma CJ, Yeh Y, Tsai HL, Huang CW, et al. Neoadjuvant FOLFOX chemotherapy combined with radiotherapy followed by radical resection in patients with locally advanced colon cancer. Radiat Oncol. 2017;12(1):48.CrossRef Huang CM, Huang MY, Ma CJ, Yeh Y, Tsai HL, Huang CW, et al. Neoadjuvant FOLFOX chemotherapy combined with radiotherapy followed by radical resection in patients with locally advanced colon cancer. Radiat Oncol. 2017;12(1):48.CrossRef
31.
Zurück zum Zitat Koizumi M, Yamada T, Shinji S, Yokoyama Y, Takahashi G, Iwai T, et al. Feasibility of neoadjuvant FOLFOX therapy without radiotherapy for baseline resectable rectal cancer. In Vivo. 2018;32(4):937–43.CrossRef Koizumi M, Yamada T, Shinji S, Yokoyama Y, Takahashi G, Iwai T, et al. Feasibility of neoadjuvant FOLFOX therapy without radiotherapy for baseline resectable rectal cancer. In Vivo. 2018;32(4):937–43.CrossRef
32.
Zurück zum Zitat Zhou J, Guo Z, Yu W, Li S, Qiao W. Clinical evaluation of preoperative radiotherapy combined with FOLFOX chemotherapy on patients with locally advanced colon cancer. Am Surg. 2019;85(4):313–20.CrossRef Zhou J, Guo Z, Yu W, Li S, Qiao W. Clinical evaluation of preoperative radiotherapy combined with FOLFOX chemotherapy on patients with locally advanced colon cancer. Am Surg. 2019;85(4):313–20.CrossRef
Metadaten
Titel
Mefenamic acid as a promising therapeutic medicine against colon cancer in tumor-bearing mice
verfasst von
Reza Seyyedi
Fereshteh Talebpour Amiri
Soghra Farzipour
Ehsan Mihandoust
Seyed Jalal Hosseinimehr
Publikationsdatum
01.02.2022
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2022
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-021-01618-3

Weitere Artikel der Ausgabe 2/2022

Medical Oncology 2/2022 Zur Ausgabe

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

16.05.2024 alpha-1-Rezeptorantagonisten Nachrichten

Nach einer Prostatabiopsie treten häufig Probleme beim Wasserlassen auf. Ob sich das durch den periinterventionellen Einsatz von Alphablockern verhindern lässt, haben australische Mediziner im Zuge einer Metaanalyse untersucht.

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

16.05.2024 Zielgerichtete Therapie Nachrichten

Trastuzumab deruxtecan scheint auch jenseits von Lungenkrebs gut gegen solide Tumoren mit HER2-Mutationen zu wirken. Dafür sprechen die Daten einer offenen Pan-Tumor-Studie.

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

15.05.2024 Mammakarzinom Nachrichten

Frauen mit lokalem oder metastasiertem Brustkrebs, die Statine einnehmen, haben eine niedrigere krebsspezifische Mortalität als Patientinnen, die dies nicht tun, legen neue Daten aus den USA nahe.

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

13.05.2024 Pankreaskarzinom Nachrichten

Gerade bei aggressiven Malignomen wie dem duktalen Adenokarzinom des Pankreas könnte Früherkennung die Therapiechancen verbessern. Noch jedoch klafft hier eine Lücke. Ein Studienteam hat einen Weg gesucht, sie zu schließen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.