Hesperidin triggering apoptosis on neuroblastoma cell

Yıl 2018, Cilt: 3 Sayı:3, 123 - 126, 30.11.2018

Tolga Çatmakaş Barış Ertuğrul Elif Sinem İplik , Bedia Çakmakoğlu

https://doi.org/10.25000/acem.449087

Cited By: 1

Öz

Aim: Neuroblastoma accounts for approximately %10
of all pediatric cancers and approximately %15 of cancer related deaths in
children. Understanding of the molecular mechanisms which play role in the
progress of this cancer type may lead to develop more effective strategies for
therapy. Flavanoids are popular subject for this new strategies. Hesperidin is an
herbal flavonoid which is found abundantly in citrus that has been studied on
several cancer cell lines. For this purpose, it was aimed to investigate is the
apoptotic effects of hesperidin on neuroblastoma tumors using SH-SY5Y cell line.

Methods: Hesperidin
was performed on SH-SY5Y and MRC-5 cell line by WST-1, Caspase-3 and
Annexin V in a time and dose dependent manner.

Results: 2.5 µM hesperidin and 5 µM hesperidin were
found the most suitable dosage for neuroblastoma cell line because of the
success on decreasing cell proliferation. Hesperidin has resulted with the
ability for apoptotic cell death compared with control group [MRC-5 cell line,
p<0.05 for all]. 2,5 µM and 5 µM hesperidin concentration for 48h were ended
up early apoptotic results as 53.65% for 2.5 µM and 38.90% for 5 µM. There was
no significant change on caspase-3 activity.

Conclusions: Our study suggests that hesperidin would be effective
against neuroblastoma tumors. We believe with further investigation this study
will be helpful for developing new research areas in neuroblastoma tumors.

Anahtar Kelimeler

Hesperidin, neuroblastoma, apoptosis

Nöroblastoma hücrelerinde hesperidinin apoptozu tetiklemesi

Öz

Amaç: Çocukluk
çağında rastlanan pediatrik kanserlerin yaklaşık %10’luk bir kısmını oluşturan nöroblastoma,
çocuklarda kansere bağlı ölümlerin yaklaşık %15’lik bir bölümünden de sorumludur.
Bu kanser türünün ilerlemesi esnasında rol alan moleküler olayların anlaşılması,
tedavi açısından daha etkili yöntemlerin ortaya konmasına aracılık
edebilecektir. Hesperidin turunçgillerde bolca bulunan bir flavonoiddir. Bu
amaçla, literatürde ilk olarak SH-SY5Y hücre hattı ve hesperidinin olası apoptotik
etkisini gösteren çalışma özelliği taşımaktadır.

Yöntem:
Hesperidinin SH-SY5Y hücre proliferasyonu ve canlılığı üzerinde doz bağımlı
etkisi için WST-1, kaspaz enzim aktivitesinin değerlendirilmesi için Kaspaz
3/BCA ve apoptotik değerlendirme için Annexin V analizleri yapılmıştır.

Bulgular: 2,5 µM hesperidin ve 5 µM hesperidin hücre
proliferasyonu üzerinde azalma etkisi yarattığından hücre hattında uygulanmak
üzere seçilmiştir. Hesperidin kontrol grubuna göre nöroblastoma üzerinde
apoptotik hücre ölümüne neden olmuştur [MRC-5 hücre hattı, hepsi için p<0.05].
2,5 µM hesperidin ve 5 µM hesperidin 48 saatlik inkübasyon sonucu %53,65 2,5 µM
için ve %38,90 5 µM için apoptoz ile sonuçlanmıştır. Kaspaz 3 aktivitesinde ise
herhangi bir değişim gözlenmemiştir.

Sonuç: Bu çalışmamızda elde ettiğimiz sonuçlardan,
nöroblastoma tümörlerinde hesperidinin antikarsinojenik etki gösterdiği
izlenimi edinilmiştir. Elde edilen verilerden yola çıkarak, çalışmamızın
yapılacak ileri araştırmalar ile birlikte nöroblastoma tümörlerinde yeni
araştırma alanlarının oluşmasında katkısı olabileceğini düşünmekteyiz.

Anahtar Kelimeler

nöroblastoma, hesperidin, apoptoz

Kaynakça

• 1. Ploessl C, Pan A, Maples KT, Lowe DK. Dinutuximab An Anti-GD2 Monoclonal Antibody for High-Risk Neuroblastoma. Ann Pharmacother. 2016;50:416-22.
• 2. London W, Castleberry RP, Matthay KK, Look AT, Seeger RC, Shimada H, et al. Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group. J Clin Oncol. 2005;23:6459-65.
• 3. Irwin MS, Park JR. Neuroblastoma: paradigm for precision medicine. Pediatr Clin North Am. 2015;62:225-56.
• 4. Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, Ambros PF, et al. Advances in risk classification and treatment strategies for neuroblastoma. J Clin Oncol. 2015;33:3008-17.
• 5. Schrey D, Vaidya SJ, Levine D, Pearson AD, Moreno L. Additional Therapies to Improve Metastatic Response to Induction Therapy in Children With High-risk Neuroblastoma. J Pediatr Hematol Oncol. 2015;37:e150-e153.
• 6. Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. New Engl J Med. 1999;341:1165-73.
• 7. Keshelava N, Seeger RC, Groshen S, Reynolds CP. Drug resistance patterns of human neuroblastoma cell lines derived from patients at different phases of therapy. Cancer Res. 1998;58:5396-405.
• 8. Xiu LJ, Sun DZ, Jiao JP, Yan B, Qin ZF, Liu X et al. Anticancer effects of traditional Chinese herbs with phlegm-eliminating properties–An overview. J Ethnopharmacol. 2015;172:155-61.
• 9. Roohbakhsh A, Parhiz H, Soltani F, Rezaee R, Iranshahi M. Neuropharmacological properties and pharmacokinetics of the citrus flavonoids hesperidin and hesperetin—a mini-review. Life Sci. 2014;113:1-6.
• 10. Agrawal YO, Sharma PK, Shrivastava B, Ojha S, Upadhya HM, Arya DS et al. Hesperidin produces cardioprotective activity via PPAR-γ pathway in ischemic heart disease model in diabetic rats. PloS One 2014;9:e111212.
• 11. Chen MC, Ye YY, Ji G, Liu JW. Hesperidin upregulates heme oxygenase-1 to attenuate hydrogen peroxide-induced cell damage in hepatic L02 cells. J Agric Food Chem. 2010;58:3330-5.
• 12. Meiyanto E, Hermawan A, Anindyajati A. Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents. Asian Pac J Cancer Prev. 2012;13:427-36.
• 13. Lv X, Zhao S, Ning Z, Zeng H, Shu Y, Tao O et al. Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health. Chemistry Central Journal. 2015;9:1-14.
• 14. Scalbert A. Zamora-Ros R. Bridging evidence from observational and intervention studies to identify flavonoids most protective for human health. Am J Clin Nutr. 2015;101:897-8.
• 15. Choi EJ, Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: involvement of CDK4 and p21. Nutr Cancer. 2007;59:115-9.
• 16. Nazari M, Ghorbani A, Hekmat-Doost A, Jeddi-Tehrani M, Zand H. Inactivation of nuclear factor-κB by citrus flavanone hesperidin contributes to apoptosis and chemo-sensitizing effect in Ramos cells. Eur J Pharmacol. 2011;650:526-33.
• 17. Ghorbani A, Nazari M, Jeddi-Tehrani M, Zand H. The citrus flavonoid hesperidin induces p53 and inhibits NF-κB activation in order to trigger apoptosis in NALM-6 cells: involvement of PPARγ-dependent mechanism. Eur J Nutr. 2012;51:39-46.
• 18. Febriansah R, Putri DD, Sarmoko, Nurulita NA, Meiyanto E, Nugroho AE. Hesperidin as a preventive resistance agent in MCF–7 breast cancer cells line resistance to doxorubicin. Asian Pac J Trop Biomed. 2014;4(3):228-233.
• 19. Yumnam S, Park HS, Kim MK, Nagappan A, Hong GE, Lee HJ, et al. Hesperidin induces paraptosis like cell death in hepatoblatoma, HepG2 cells: Involvement of ERK1/2 MAPK. PloS One. 2014;9:e101321.
• 20. Tamilselvam K, Braidy N, Manivasagam T, Essa MM, Prasad NR, Karthikeyan S, et al. Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson’s disease. Oxidative Medicine and Cellular Longevity. 2013;2013.
• 21. Dourado GK, Stanilka JM, Percival SS, Cesar TB. Chemopreventive Actions of Blond and Red-Fleshed Sweet Orange Juice on the Loucy Leukemia Cell Line. Asian Pac J Cancer Prev. 2015;16:6491-9.