Araştırma Makalesi
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Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif ve Apoptotik Etkilerinin Belirlenmesi

Yıl 2021, Cilt: 16 Sayı: 1, 80 - 87, 26.04.2021

Öz

Gastrik karsinoma yüksek morbidite ve mortalite ile insanlarda ve hayvanlarda görülen bir kanser türüdür. Gossypin Hibiscus vitifolius'tan izole edilen doğal bir flavonoid grubunda doğal bir maddedir. Bu çalışmada gossypin’in Kato-III gastrik karsinoma hücrelerinde anti-proliferatif ve apoptotik etkilerinin araştırılması amaçlanmıştır. Kato-III hücreleri uygun ortamlarda kültüre edildi ve gossypin’in etkin doz aralığı (5-100 μg/ml) ve hücre canlılığı üzerindeki etkileri MTT testi ile 24, 48 ve 72. saatlerde tespit edildi. RT-PCR yöntemi ile kaspaz-3, 9 ve NF-kB gen ekspresyonları belirlendi. Floresan boyama tekniği ile apoptoz seviyeleri tespit edildi. Sisplatin pozitif kontrol grubu olarak deney eklendi. Gossypin’in Kato-III hücre proliferasyonunu doza ve zamana bağlı olarak azalttığı tespit edildi. Gossypin kaspaz-3 ve kaspaz-9 seviyelerini artırırken NF-kB seviyelerini inhibe ettiği ve sonuçların sisplatin ile benzerlik gösterdiği tespit edildi. Hücre morfolojik analiz ve floresan boyama sonuçlarına göre gossypin 100 μg/ml dozunda apoptozu en fazla artıran grup olduğu gösterilmiştir. Sonuç olarak gossypin’in gastrik karsinoma hücrelerinde apoptozu aktive ettiği ve tedavide potansiyel bir aday olabileceği ortaya konmuştur.

Kaynakça

  • 1. Elliott GS., Stoffregen DA., Richardson DC., Blevins WE., Richardson RC., 1984. Surgical, medical, and nutritional management of gastric adenocarcinoma in a dog. J Am Vet Med Assoc, 185, 98-101.
  • 2. Lingeman CH., Garner F., Taylor DO., 1971. Spontaneous gastric adenocarcinomas of dogs: a review. J Natl Cancer Inst, 47, 137-153.
  • 3. Gualtieri M., Monzeglio MG., Scanziani E., 1999. Gastric neoplasia. Vet Clin North Am Small Anim Pract, 29, 415-440.
  • 4. Fox JG., Wang TC., 2007. Inflammation, atrophy, and gastric cancer. J Clin Invest, 117, 60-69.
  • 5. Hamashima C., 2014. Current issues and future perspectives of gastric cancer screening. World J Gastroenterol, 20, 13767.
  • 6. Ishibashi M., Ohtsuki T., 2008. Studies on search for bioactive natural products targeting TRAIL signaling leading to tumor cell apoptosis. Med Res Rev, 28, 688-714.
  • 7. Babu B., Jayram H., Nair M., Ajaikumar K., Padikkala J. 2003. Free radical scavenging, antitumor and anticarcinogenic activity of gossypin. J Exp Clin Cancer Res, 22, 581-589.
  • 8. Wang L., Wang X., Chen H., Zu X., Ma F., Liu K., Bode AM., Dong Z., Kim DJ. 2019. Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2. Phytother Res, 33, 640-650.
  • 9. Portt L., Norman G., Clapp C., Greenwood M., Greenwood MT., 2011. Anti-apoptosis and cell survival: a review. Biochim Biophys Acta Mol Cell Res, 1813, 238-259.
  • 10. Chen M., Wang J., 2002. Initiator caspases in apoptosis signaling pathways. Apoptosis, 7, 313-319.
  • 11. Salvesen GS., Dixit VM., 1997. Caspases: intracellular signaling by proteolysis. Cell, 91, 443-446.
  • 12. Frejlich E., Rudno-Rudzinska J., Janiszewski K., Salomon L., Kotulski K., Pelzer O., Grzebieniak Z., Tarnawa R., Kielan W., 2013. Caspases and their role in gastric cancer. Adv Clin Exp Med, 22, 593-602.
  • 13. Sun Y., Chen XY., Liu J., Cheng XX., Wang XW., Kong QY., Li H., 2006. Differential caspase-3 expression in noncancerous, premalignant and cancer tissues of stomach and its clinical implication. Cancer Detect Prev, 30, 168-173.
  • 14. Li YH., Wang C., Meng K., Chen LB., Zhou XJ., 2004. Influence of survivin and caspase-3 on cell apoptosis and prognosis in gastric carcinoma. World J Gastroenterol, 10, 1984-1988.
  • 15. Cinar I., 2020. Apoptosis-Inducing Activity and Antiproliferative Effect of Gossypin on PC-3 Prostate Cancer Cells. Anticancer Agents Med Chem, 21, 445-450.
  • 16. Demirkaya AK., Gündoğdu G., Dodurga Y., Seçme M., Gündoğdu K., 2019. Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik ve Genotoksik Etkisinin Belirlenmesi. Atatürk Üniversitesi Vet Bil Derg, 14, 29-37.
  • 17. Cinar I., Yayla M., Binnetoglu D., 2020. Antiproliferative effect of gossypin on human hepatoma (Hep-3B) cells. Cukurova Med J, 45, 1165-1172.
  • 18. Demir R., Cadirci E., Akpinar E., Cayir Y., Atmaca HT., Un H., Kunak CS., Yayla M., Bayraktutan Z., Demir I., 2015. Does bosentan protect diabetic brain alterations in rats? The role of endothelin-1 in the diabetic brain. Basic Clin Pharmacol Toxicol, 116, 236-243.
  • 19. Duygu K., Halıcı Z., Toktay E., 2020. Prepubertal ve Postpubertal Sıçanların Genital Sistem Organlarında Ürotensin 2 Reseptörünün Karşılaştırılması. Atatürk Üniversitesi Vet Bil Derg, 15, 113-121.
  • 20. Bayir Y., Un H., Cadirci E., Akpinar E., Diyarbakir B., Calik I., Halici Z., 2019. Effects of Aliskiren, an RAAS inhibitor, on a carrageenan-induced pleurisy model of rats. An Acad Bras Cienc, 91, e20180106.
  • 21. Spirina LV., Avgustinovich AV., Afanas'ev SG., Cheremisina OV., Volkov MY., Choynzonov EL., Gorbunov AK., Usynin EA., 2020. Molecular mechanism of resistance to chemotherapy in gastric cancers, the role of autophagy. Curr Drug Targets, 21, 713-721.
  • 22. Homayoun M., Ghasemnezhad Targhi R., Soleimani M., 2020. Anti-proliferative and anti-apoptotic effects of grape seed extract on chemo-resistant OVCAR-3 ovarian cancer cells. Res Pharm Sci, 15, 390-400.
  • 23. Zhang Z., Yang L., Hou J., Tian S., Liu Y., 2020. Molecular mechanisms underlying the anticancer activities of licorice flavonoids. J Ethnopharmacol, 267, 113635.
  • 24. Debatin KM., 2004. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immunother, 53, 153-159.
  • 25. Yi CH., Yuan J., 2009. The Jekyll and Hyde functions of caspases. Dev Cell, 16, 21-34.
  • 26. Savva CG., Totokotsopoulos S., Nicolaou KC., Neophytou CM., Constantinou AI., 2016. Selective activation of TNFR1 and NF-κB inhibition by a novel biyouyanagin analogue promotes apoptosis in acute leukemia cells. BMC Cancer, 16, 279.
  • 27. Fu YG., Qu YJ., Wu KC., Zhai HH., Liu ZG., Fan D-M. 2003. Apoptosis-inducing effect of recombinant Caspase-3 expressed by constructed eukaryotic vector on gastric cancer cell line SGC7901. World J Gastroenterol, 9, 1935.
  • 28. Jiang XH., Chun‐Yu Wong B., Yuen ST., Jiang SH., Cho CH., Lai KC., Lin MC., Kung HF., Lam SK., 2001. Arsenic trioxide induces apoptosis in human gastric cancer cells through up‐regulation of P53 and activation of caspase‐3. Int J Cancer, 91, 173-179.
  • 29. Dolcet X., Llobet D., Pallares J., Matias-Guiu X., 2005. NF-kB in development and progression of human cancer. Virchows archiv, 446, 475-482.
  • 30. Wang C-Y., Mayo MW., Baldwin AS., 1996. TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science, 274, 784-787.
  • 31. De Simone V., Franze E., Ronchetti G., Colantoni A., Fantini M., Di Fusco D., Sica G., Sileri P., MacDonald T., Pallone F., 2015. Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene, 34, 3493-3503.
  • 32. Frelin C., Imbert V., Bottero V., Gonthier N., Samraj AK., Schulze-Osthoff K., Auberger P., Courtois G., Peyron JF., 2008. Inhibition of the NF-kappaB survival pathway via caspase-dependent cleavage of the IKK complex scaffold protein and NF-kappaB essential modulator NEMO. Cell Death Differ, 15, 152-160.
  • 33. Scheidereit C., 2006. IκB kinase complexes: gateways to NF-κ B activation and transcription. Oncogene, 25, 6685-6705.
  • 34. Pomerantz JL., Baltimore D., 2002. Two pathways to NF-κB. Molecular cell, 10, 693-695.
  • 35. Hazafa A., Rehman KU., Jahan N., Jabeen Z., 2020. The role of polyphenol (Flavonoids) compounds in the treatment of cancer cells. Nutr Cancer, 72, 386-397.
  • 36. Priyadarsini RV., Murugan RS., Maitreyi S., Ramalingam K., Karunagaran D., Nagini S., 2010. The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur J Pharmacol, 649, 84-91.
  • 37. Yoshimizu N., Otani Y., Saikawa Y., Kubota T., Yoshida M., Furukawa T., Kumai K., Kameyama K., Fujii M., Yano M., 2004. Anti‐tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation. Aliment Pharmacol Ther, 20, 95-101.
  • 38. Chiu CT., Chen JH., Chou FP., Lin HH., 2015. Hibiscus sabdariffa leaf extract inhibits human prostate cancer cell invasion via down-regulation of Akt/NF-kB/MMP-9 pathway. Nutrients, 7, 5065-5087.

Investigation of Anti-Proliferative and Apoptotic Effects of Gossypin in Kato-III Cells

Yıl 2021, Cilt: 16 Sayı: 1, 80 - 87, 26.04.2021

Öz

Gastric carcinoma is a type of cancer in humans and animals with high morbidity and mortality. Gossypin is a natural flavonoid group isolated from Hibiscus vitifolius. In this study, it was aimed to investigate the anti-proliferative and apoptotic effects of gossypin in Kato-III cells. Cells were cultured in standard culture conditions. Cell viability and the effective dose range (5-100 μg/ml) of gossypin were determined at 24, 48 and 72nd hours by MTT. Caspase-3, 9, and NF-kB gene expressions were determined by Real Time-PCR method. Apoptosis levels were determined by fluorescent staining method. Cisplatin was used as positive control group. It was determined that Gossypin decreased Kato-III cell proliferation depending on the dose and time. Gossypin was found to increase caspase-3 and caspase-9 levels while inhibiting NF-kB levels, and the results were similar to cisplatin. Fluorescent staining results showed that gossypin increased apoptosis. As a result, it has been revealed that gossypin activates apoptosis in gastric carcinoma cells and may be a potential candidate for treatment.

Kaynakça

  • 1. Elliott GS., Stoffregen DA., Richardson DC., Blevins WE., Richardson RC., 1984. Surgical, medical, and nutritional management of gastric adenocarcinoma in a dog. J Am Vet Med Assoc, 185, 98-101.
  • 2. Lingeman CH., Garner F., Taylor DO., 1971. Spontaneous gastric adenocarcinomas of dogs: a review. J Natl Cancer Inst, 47, 137-153.
  • 3. Gualtieri M., Monzeglio MG., Scanziani E., 1999. Gastric neoplasia. Vet Clin North Am Small Anim Pract, 29, 415-440.
  • 4. Fox JG., Wang TC., 2007. Inflammation, atrophy, and gastric cancer. J Clin Invest, 117, 60-69.
  • 5. Hamashima C., 2014. Current issues and future perspectives of gastric cancer screening. World J Gastroenterol, 20, 13767.
  • 6. Ishibashi M., Ohtsuki T., 2008. Studies on search for bioactive natural products targeting TRAIL signaling leading to tumor cell apoptosis. Med Res Rev, 28, 688-714.
  • 7. Babu B., Jayram H., Nair M., Ajaikumar K., Padikkala J. 2003. Free radical scavenging, antitumor and anticarcinogenic activity of gossypin. J Exp Clin Cancer Res, 22, 581-589.
  • 8. Wang L., Wang X., Chen H., Zu X., Ma F., Liu K., Bode AM., Dong Z., Kim DJ. 2019. Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2. Phytother Res, 33, 640-650.
  • 9. Portt L., Norman G., Clapp C., Greenwood M., Greenwood MT., 2011. Anti-apoptosis and cell survival: a review. Biochim Biophys Acta Mol Cell Res, 1813, 238-259.
  • 10. Chen M., Wang J., 2002. Initiator caspases in apoptosis signaling pathways. Apoptosis, 7, 313-319.
  • 11. Salvesen GS., Dixit VM., 1997. Caspases: intracellular signaling by proteolysis. Cell, 91, 443-446.
  • 12. Frejlich E., Rudno-Rudzinska J., Janiszewski K., Salomon L., Kotulski K., Pelzer O., Grzebieniak Z., Tarnawa R., Kielan W., 2013. Caspases and their role in gastric cancer. Adv Clin Exp Med, 22, 593-602.
  • 13. Sun Y., Chen XY., Liu J., Cheng XX., Wang XW., Kong QY., Li H., 2006. Differential caspase-3 expression in noncancerous, premalignant and cancer tissues of stomach and its clinical implication. Cancer Detect Prev, 30, 168-173.
  • 14. Li YH., Wang C., Meng K., Chen LB., Zhou XJ., 2004. Influence of survivin and caspase-3 on cell apoptosis and prognosis in gastric carcinoma. World J Gastroenterol, 10, 1984-1988.
  • 15. Cinar I., 2020. Apoptosis-Inducing Activity and Antiproliferative Effect of Gossypin on PC-3 Prostate Cancer Cells. Anticancer Agents Med Chem, 21, 445-450.
  • 16. Demirkaya AK., Gündoğdu G., Dodurga Y., Seçme M., Gündoğdu K., 2019. Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik ve Genotoksik Etkisinin Belirlenmesi. Atatürk Üniversitesi Vet Bil Derg, 14, 29-37.
  • 17. Cinar I., Yayla M., Binnetoglu D., 2020. Antiproliferative effect of gossypin on human hepatoma (Hep-3B) cells. Cukurova Med J, 45, 1165-1172.
  • 18. Demir R., Cadirci E., Akpinar E., Cayir Y., Atmaca HT., Un H., Kunak CS., Yayla M., Bayraktutan Z., Demir I., 2015. Does bosentan protect diabetic brain alterations in rats? The role of endothelin-1 in the diabetic brain. Basic Clin Pharmacol Toxicol, 116, 236-243.
  • 19. Duygu K., Halıcı Z., Toktay E., 2020. Prepubertal ve Postpubertal Sıçanların Genital Sistem Organlarında Ürotensin 2 Reseptörünün Karşılaştırılması. Atatürk Üniversitesi Vet Bil Derg, 15, 113-121.
  • 20. Bayir Y., Un H., Cadirci E., Akpinar E., Diyarbakir B., Calik I., Halici Z., 2019. Effects of Aliskiren, an RAAS inhibitor, on a carrageenan-induced pleurisy model of rats. An Acad Bras Cienc, 91, e20180106.
  • 21. Spirina LV., Avgustinovich AV., Afanas'ev SG., Cheremisina OV., Volkov MY., Choynzonov EL., Gorbunov AK., Usynin EA., 2020. Molecular mechanism of resistance to chemotherapy in gastric cancers, the role of autophagy. Curr Drug Targets, 21, 713-721.
  • 22. Homayoun M., Ghasemnezhad Targhi R., Soleimani M., 2020. Anti-proliferative and anti-apoptotic effects of grape seed extract on chemo-resistant OVCAR-3 ovarian cancer cells. Res Pharm Sci, 15, 390-400.
  • 23. Zhang Z., Yang L., Hou J., Tian S., Liu Y., 2020. Molecular mechanisms underlying the anticancer activities of licorice flavonoids. J Ethnopharmacol, 267, 113635.
  • 24. Debatin KM., 2004. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immunother, 53, 153-159.
  • 25. Yi CH., Yuan J., 2009. The Jekyll and Hyde functions of caspases. Dev Cell, 16, 21-34.
  • 26. Savva CG., Totokotsopoulos S., Nicolaou KC., Neophytou CM., Constantinou AI., 2016. Selective activation of TNFR1 and NF-κB inhibition by a novel biyouyanagin analogue promotes apoptosis in acute leukemia cells. BMC Cancer, 16, 279.
  • 27. Fu YG., Qu YJ., Wu KC., Zhai HH., Liu ZG., Fan D-M. 2003. Apoptosis-inducing effect of recombinant Caspase-3 expressed by constructed eukaryotic vector on gastric cancer cell line SGC7901. World J Gastroenterol, 9, 1935.
  • 28. Jiang XH., Chun‐Yu Wong B., Yuen ST., Jiang SH., Cho CH., Lai KC., Lin MC., Kung HF., Lam SK., 2001. Arsenic trioxide induces apoptosis in human gastric cancer cells through up‐regulation of P53 and activation of caspase‐3. Int J Cancer, 91, 173-179.
  • 29. Dolcet X., Llobet D., Pallares J., Matias-Guiu X., 2005. NF-kB in development and progression of human cancer. Virchows archiv, 446, 475-482.
  • 30. Wang C-Y., Mayo MW., Baldwin AS., 1996. TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science, 274, 784-787.
  • 31. De Simone V., Franze E., Ronchetti G., Colantoni A., Fantini M., Di Fusco D., Sica G., Sileri P., MacDonald T., Pallone F., 2015. Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene, 34, 3493-3503.
  • 32. Frelin C., Imbert V., Bottero V., Gonthier N., Samraj AK., Schulze-Osthoff K., Auberger P., Courtois G., Peyron JF., 2008. Inhibition of the NF-kappaB survival pathway via caspase-dependent cleavage of the IKK complex scaffold protein and NF-kappaB essential modulator NEMO. Cell Death Differ, 15, 152-160.
  • 33. Scheidereit C., 2006. IκB kinase complexes: gateways to NF-κ B activation and transcription. Oncogene, 25, 6685-6705.
  • 34. Pomerantz JL., Baltimore D., 2002. Two pathways to NF-κB. Molecular cell, 10, 693-695.
  • 35. Hazafa A., Rehman KU., Jahan N., Jabeen Z., 2020. The role of polyphenol (Flavonoids) compounds in the treatment of cancer cells. Nutr Cancer, 72, 386-397.
  • 36. Priyadarsini RV., Murugan RS., Maitreyi S., Ramalingam K., Karunagaran D., Nagini S., 2010. The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur J Pharmacol, 649, 84-91.
  • 37. Yoshimizu N., Otani Y., Saikawa Y., Kubota T., Yoshida M., Furukawa T., Kumai K., Kameyama K., Fujii M., Yano M., 2004. Anti‐tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation. Aliment Pharmacol Ther, 20, 95-101.
  • 38. Chiu CT., Chen JH., Chou FP., Lin HH., 2015. Hibiscus sabdariffa leaf extract inhibits human prostate cancer cell invasion via down-regulation of Akt/NF-kB/MMP-9 pathway. Nutrients, 7, 5065-5087.
Toplam 38 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makaleleri
Yazarlar

Harun Ün 0000-0003-1772-282X

Rüstem Anıl Ugan 0000-0002-4837-2343

İrfan Çınar 0000-0002-9826-2556

Yayımlanma Tarihi 26 Nisan 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 16 Sayı: 1

Kaynak Göster

APA Ün, H., Ugan, R. A., & Çınar, İ. (2021). Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif ve Apoptotik Etkilerinin Belirlenmesi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 16(1), 80-87.
AMA Ün H, Ugan RA, Çınar İ. Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif ve Apoptotik Etkilerinin Belirlenmesi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. Nisan 2021;16(1):80-87.
Chicago Ün, Harun, Rüstem Anıl Ugan, ve İrfan Çınar. “Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif Ve Apoptotik Etkilerinin Belirlenmesi”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 16, sy. 1 (Nisan 2021): 80-87.
EndNote Ün H, Ugan RA, Çınar İ (01 Nisan 2021) Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif ve Apoptotik Etkilerinin Belirlenmesi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 16 1 80–87.
IEEE H. Ün, R. A. Ugan, ve İ. Çınar, “Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif ve Apoptotik Etkilerinin Belirlenmesi”, Atatürk Üniversitesi Veteriner Bilimleri Dergisi, c. 16, sy. 1, ss. 80–87, 2021.
ISNAD Ün, Harun vd. “Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif Ve Apoptotik Etkilerinin Belirlenmesi”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 16/1 (Nisan 2021), 80-87.
JAMA Ün H, Ugan RA, Çınar İ. Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif ve Apoptotik Etkilerinin Belirlenmesi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. 2021;16:80–87.
MLA Ün, Harun vd. “Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif Ve Apoptotik Etkilerinin Belirlenmesi”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, c. 16, sy. 1, 2021, ss. 80-87.
Vancouver Ün H, Ugan RA, Çınar İ. Gossypin’in Kato-III Hücrelerindeki Anti-Proliferatif ve Apoptotik Etkilerinin Belirlenmesi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. 2021;16(1):80-7.