본문 바로가기
KERD
논문KCI 등재

Autophagy Inhibition Promotes Quercetin Induced Apoptosis in MG-63 Human Osteosarcoma cells

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류치의학

초록

Quercetin is a natural flavonoid phytochemical that is extracted from various plants. Having an advantages due to its varied biological properties, such as anti-inflammatory, anti-viral, anti-oxidant, and anti-cancer effects, quercetin is used to treat many diseases. Recently, it has been reported that autophagy inhibition may play a key role in anti-cancer therapy. Therefore, in this study, we investigated the molecular mechanisms and anti-cancer effects of quercetin in human osteosarcoma cells via autophagy inhibition. We ascertained that quercetin inhibited cell proliferation and induced cell death, these process is demonstrated that apoptosis via the mitochondrial pathway and the caspase cascade. Quercetin also induced autophagy which was inhibited by 3-MA, autophagy inhibitor and the blockade of autophagy promoted the quercetin-induced apoptosis, confirming that autophagy is a pro-survival process. Thus, these findings demonstrate that quercetin is an effective anti-cancer agent, and the combination of quercetin and an autophagy inhibitor should enhance the effect of anti-cancer therapy.

Abstract

Quercetin is a natural flavonoid phytochemical that is extracted from various plants. Having an advantages due to its varied biological properties, such as anti-inflammatory, anti-viral, anti-oxidant, and anti-cancer effects, quercetin is used to treat many diseases. Recently, it has been reported that autophagy inhibition may play a key role in anti-cancer therapy. Therefore, in this study, we investigated the molecular mechanisms and anti-cancer effects of quercetin in human osteosarcoma cells via autophagy inhibition. We ascertained that quercetin inhibited cell proliferation and induced cell death, these process is demonstrated that apoptosis via the mitochondrial pathway and the caspase cascade. Quercetin also induced autophagy which was inhibited by 3-MA, autophagy inhibitor and the blockade of autophagy promoted the quercetin-induced apoptosis, confirming that autophagy is a pro-survival process. Thus, these findings demonstrate that quercetin is an effective anti-cancer agent, and the combination of quercetin and an autophagy inhibitor should enhance the effect of anti-cancer therapy.

참고문헌 (25)

  1. Broadhead ML, "The molecular pathogenesis of osteosarcoma: a review", Sarcoma, 2011, pp.959248~ (2011)[DOI]
  2. Yu Nagai, "Phototoxic effect of na-pheophorbide a toward osteosarcoma cells in vitro using a laser diode", Photomedicine and Laser Surgery, 32(9), pp.481~489 (2014), Mary Ann Liebert Inc[DOI]
  3. Lamoureux F, "Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma", Oncotarget, 5(17), pp.7805~7819 (2014)
  4. Isabel Correia, "Effects of Naproxen on Cell Proliferation and Genotoxicity in MG-63 Osteosarcoma Cell Line", Journal of Toxicology and Environmental Health, Part A, 77(14-16), pp.916~923 (2014), Informa UK Limited[DOI]
  5. Dominique Heymann, "Targeted therapies for bone sarcomas", BoneKEy Reports, 2 (2013), Springer Nature[DOI]
  6. Naruse T, "Meloxicam inhibits osteosarcoma growth, invasiveness and metastasis by COX-2-dependent and independent routes", Carcinogenesis, 27, pp.584~592 (2006)
  7. E. Sugantha Priya, "Anti-cancer activity of quercetin in neuroblastoma: an in vitro approach", Neurological Sciences, 35(2), pp.163~170 (2014), Springer Nature[DOI]
  8. Wei Li, "Effects of quercetin on hedgehog signaling in chronic myeloid leukemia KBM7 cells", Chinese Journal of Integrative Medicine, 20(10), pp.776~781 (2014), Springer Nature[DOI]
  9. Bo-Lin Chen, "Quercetin attenuates renal ischemia", reperfusion injury via an activation of AMP-activated protein kinase-regulated autophagy pathway, 2014, pp.25(11), 1226~1234[DOI]
  10. Wei-Jiunn Lee, "Quercetin induces mitochondrial-derived apoptosis via reactive oxygen species-mediated ERK activation in HL-60 leukemia cells and xenograft", Archives of Toxicology, 89(7), pp.1103~1117 (2015), Springer Nature[DOI]
  11. Wu X, "Quercetin promotes proliferation and differentiation of oligodendrocyte precursor cells after oxygen", glucose deprivation-induced injury, 2014, pp.34, 463~471
  12. Li Y, "Flavonoids from tartary buckwheat induce G2", M cell cycle arrest and apoptosis in human hepatoma HepG2 cells, 2014, pp.46, 460~470
  13. 이주현, "Effect of quercetin on apoptosis of PANC-1 cells", 대한외과학회지, 85(6), pp.249~260 (2013), 대한외과학회
  14. Hui-Hui Cao, "Quercetin exerts anti-melanoma activities and inhibits STAT3 signaling", Biochemical Pharmacology, 87(3), pp.424~434 (2014), Elsevier BV[DOI]
  15. Youn H, "Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells", Biol Pharm Bull, 36, pp.944~951 (2013)
  16. Shen-Jeu Won, "Justicidin A-Induced Autophagy Flux Enhances Apoptosis of Human Colorectal Cancer Cells via Class III PI3K and Atg5 Pathway", Journal of Cellular Physiology, 230(4), pp.930~946 (2015), Wiley-Blackwell[DOI]
  17. Guo XL, "Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation inhibition in hepatocarcinoma cells", Cancer Lett, 320, pp.171~179 (2012)
  18. Xian-ling Guo, "Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation inhibition in hepatocarcinoma cells", Cancer Letters, 320(2), pp.171~179 (2012), Elsevier BV[DOI]
  19. Annick Notte, "Autophagy as a mediator of chemotherapy-induced cell death in cancer", Biochemical Pharmacology, 82(5), pp.427~434 (2011), Elsevier BV[DOI]
  20. Psahoulia FH, "Quercetin mediates preferential degradation of oncogenic Ras and causes autophagy in Ha-RAS-transformed human colon cells", Carcinogenesis, 28, pp.1021~1031 (2007)
  21. Hail N Jr., "Apoptosis effector mechanisms : a requiem performed in different keys", Apoptosis, 11, pp.889~904 (2006)
  22. 김근태, "Quercetin Regulates Sestrin 2-AMPK-mTOR Signaling Pathway and Induces Apoptosis via Increased Intracellular ROS in HCT116 Colon Cancer Cells", 대한암예방학회지, 18(3), pp.264~270 (2013), 대한암예방학회
  23. Kim H, "Quercetin induces mitochondrial mediated apoptosis and protective autophagy in human glioblastoma U373MG cells.", Oxid Med Cell Longev, 2013, pp.596496~ (2013)[DOI]
  24. Palmeira dos Santos C, "Comparative study of autophagy inhibition by 3MA and CQ on Cytarabineinduced death of leukaemia cells", J Cancer Res Clin Oncol, 140, pp.909~920 (2014)
  25. Wang K, "Quercetin induces protective autophagy in gastric cancer cells : involvement of Akt-mTOR-and hypoxia-induced factor 1alpha-mediated signaling", Autophagy, 7, pp.966~978 (2011)

관련 논문AI추천

이 간행물의 다른 논문 (5건)