Luteolin promotes the sensitivity of cisplatin in ovarian cancer by decreasing PRPA1-medicated autophagy
Corresponding Author(s) : Yongjie Tian
Cellular and Molecular Biology,
Vol. 64 No. 6: Advances in mechanism and treatment strategy of cancer
Abstract
Luteolin (LUT) is a flavone universally presented in plants. It shows an anti-carcinogenic effect in different cancers and could increase the sensitivity of cisplatin in colorectal cancer cell lines through Nrf2 pathway. However, the effect of luteolin on the sensitivity to ovarian cancer cells has not been studied. In this study, luteolin was found to suppress autophagy with reduced expression of LC3-II, but enhanced the inhibition of cell vitality and promoted apoptosis induced by cisplatin, leading to restoration of the sensitivity to cisplatin in ovarian cancer cells through CCK-8, flow cytometry and immunofluorescent assays. Although cisplatin elevated the PARP1 for cell survival, the cisplatin-induced expression of PARP1 was inhibited by luteolin a dose- and time- dependent manner through Q-PCR and WB assays. Further, PARP1 siRNA could further improve the LUT-induced inhibition of cell vitality and restore the sensitivity to cisplatin with reduced LC3-II levels. Our present work demonstrate that LUT can suppresses autophagy but enhance apoptosis induced by cisplatin and promote the sensitivity to cisplatin through suppressing the expression of RARP1 in ovarian cancer.
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- Martin Lluesma S, Wolfer A, Harari A, Kandalaft LE. Cancer Vaccines in Ovarian Cancer: How Can We Improve? Biomedicines 2016; 4: E10.
- Tomao F, Marchetti C, Romito A, et al. Overcoming platinum resistance in ovarian cancer treatment: from clinical practice to emerging chemical therapies. Expert Opin Pharmacother 2017;
- Verdoodt F, Kjaer SK, Friis S. Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer: Summary of epidemiologic evidence of cancer risk and prognosis. Maturitas 2017; 100: 1-7.
- Hou X, Bai X, Gou X, et al. 3"²,4"²,5"²,5,7-Pentamethoxyflavone sensitizes cisplatin-resistant A549 cells to cisplatin by inhibition of Nrf2 pathway. Mol Cells 2015; 38: 396-401.
- Chakrabarti M, Ray SK. Anti-tumor activities of luteolin and silibinin in glioblastoma cells: overexpression of miR-7-1-3p augmented luteolin and silibinin to inhibit autophagy and induce apoptosis in glioblastoma in vivo. Apoptosis 2016; 21: 312-28.
- Deng L, Jiang L, Lin X, Tseng KF, Lu Z, Wang X. Luteolin, a novel p90 ribosomal S6 kinase inhibitor, suppresses proliferation and migration in leukemia cells. Oncol Lett 2017; 13: 1370-8.
- Guo YF, Xu NN, Sun W, Zhao Y, Li CY, Guo MY.Luteolin reduces inflammation in Staphylococcus aureus-induced mastitis by inhibiting NF-kB activation and MMPs expression. Oncotarget 2017; 8: 28481-93.
- Chian S, Li YY, Wang XJ, Tang XW. Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway.Asian Pac J Cancer Prev 2014; 15: 2911-6.
- Dia VP, Pangloli P. Epithelial-to-Mesenchymal transition in paclitaxel-resistant ovarian cancer cells is downregulated by luteolin. J Cell Physiol 2017; 232: 391-401.
- Lu DF, Yang LJ, Wang F, Zhang GL. Inhibitory effect of luteolin on estrogen biosynthesis in human ovarian granulosa cells by suppression of aromatase (CYP19). J Agric Food Chem 2012; 60: 8411-8.
- Bravo-San Pedro JM, Kroemer G, Galluzzi L. Autophagy and mitophagy in cardiovascular disease. Circ Res 2017; 120: 1812-24.
- Muller S, Brun S, René F, de Sèze J, Loeffler JP, Jeltsch-David H. Autophagy in neuroinflammatory diseases. Autoimmun Rev 2017; S1568-9972: 30139-8.
- Rouleau M, Patel A, Hendzel MJ, Kaufmann SH, Poirier GG. PARP inhibition: PARP1 and beyond. Nat Rev Cancer 2010; 10: 293-301.
- Mangerich A, Bürkle A. Pleiotropic cellular functions of PARP1 in longevity and aging: genome maintenance meets inflammation. Oxid Med Cell Longev 2012; 2012: 321653.
- Schiewer MJ, Knudsen KE. Transcriptional roles of PARP1 in cancer. Mol Cancer Res 2014; 12: 1069-80.
- Beck C, Robert I, Reina-San-Martin B, Schreiber V, Dantzer F. Poly(ADP-ribose) polymerases in double-strand break repair: focus on PARP1, PARP2 and PARP3. Exp Cell Res 2014; 329: 18-25.
- Malyuchenko NV, Kotova EY, Kulaeva OI, Kirpichnikov MP, Studitskiy VM. PARP1 Inhibitors: antitumor drug design. Acta Naturae, 2015; 7: 27-37.
- Singh SS, Sarma JA, Narasu L, Dayam R, Xu S, Neamati N. A review on PARP1 inhibitors: Pharmacophore modeling, virtual and biological screening studies to identify novel PARP1 inhibitors. Curr Top Med Chem 2014; 14: 2020-30.
- Mangerich A, Burkle A. Pleiotropic cellular functions of PARP1 in longevity and aging: genome maintenance meets inflammation. Oxid Med Cell Longev 2012; 2012: 321653.
- Kwon DY, Han GH, Ulak R, Ki KD, Lee JM, Lee SK. Syndrome of inappropriate antidiuretic hormone secretion following irinotecan-cisplatin administration as a treatment for recurrent ovarian clear cell carcinoma. Obstet Gynecol Sci 2017; 60: 115-7.
- Samuel P, Pink RC, Brooks SA, Carter DR. miRNAs and ovarian cancer: a miRiad of mechanisms to induce cisplatin drug resistance. Expert Rev Anticancer Ther 2016; 16: 57-70.
- Park SH, Park HS, Lee JH, et al. Induction of endoplasmic reticulum stress-mediated apoptosis and non-canonical autophagy by luteolin in NCI-H460 lung carcinoma cells. Food Chem Toxicol 2013; 56: 100-9.
- Peng M, Watanabe S, Chan KWK, et al. Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin. Antiviral Res 2017; 143: 176-185.
- Wang Q, Wang H, Jia Y, Pan H, Ding H. Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma. Cancer Chemother Pharmacol 2017; 79: 1031-
- Yan M, Liu Z, Yang H, et al. Luteolin decreases the UVA induced autophagy of human skin fibroblasts by scavenging ROS. Mol Med Rep 2016; 14: 1986-92.
- Ji Y, Tulin AV. The roles of PARP1 in gene control and cell differentiation. Curr Opin Genet Dev 2010; 20: 512-8.
References
Martin Lluesma S, Wolfer A, Harari A, Kandalaft LE. Cancer Vaccines in Ovarian Cancer: How Can We Improve? Biomedicines 2016; 4: E10.
Tomao F, Marchetti C, Romito A, et al. Overcoming platinum resistance in ovarian cancer treatment: from clinical practice to emerging chemical therapies. Expert Opin Pharmacother 2017;
Verdoodt F, Kjaer SK, Friis S. Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer: Summary of epidemiologic evidence of cancer risk and prognosis. Maturitas 2017; 100: 1-7.
Hou X, Bai X, Gou X, et al. 3"²,4"²,5"²,5,7-Pentamethoxyflavone sensitizes cisplatin-resistant A549 cells to cisplatin by inhibition of Nrf2 pathway. Mol Cells 2015; 38: 396-401.
Chakrabarti M, Ray SK. Anti-tumor activities of luteolin and silibinin in glioblastoma cells: overexpression of miR-7-1-3p augmented luteolin and silibinin to inhibit autophagy and induce apoptosis in glioblastoma in vivo. Apoptosis 2016; 21: 312-28.
Deng L, Jiang L, Lin X, Tseng KF, Lu Z, Wang X. Luteolin, a novel p90 ribosomal S6 kinase inhibitor, suppresses proliferation and migration in leukemia cells. Oncol Lett 2017; 13: 1370-8.
Guo YF, Xu NN, Sun W, Zhao Y, Li CY, Guo MY.Luteolin reduces inflammation in Staphylococcus aureus-induced mastitis by inhibiting NF-kB activation and MMPs expression. Oncotarget 2017; 8: 28481-93.
Chian S, Li YY, Wang XJ, Tang XW. Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway.Asian Pac J Cancer Prev 2014; 15: 2911-6.
Dia VP, Pangloli P. Epithelial-to-Mesenchymal transition in paclitaxel-resistant ovarian cancer cells is downregulated by luteolin. J Cell Physiol 2017; 232: 391-401.
Lu DF, Yang LJ, Wang F, Zhang GL. Inhibitory effect of luteolin on estrogen biosynthesis in human ovarian granulosa cells by suppression of aromatase (CYP19). J Agric Food Chem 2012; 60: 8411-8.
Bravo-San Pedro JM, Kroemer G, Galluzzi L. Autophagy and mitophagy in cardiovascular disease. Circ Res 2017; 120: 1812-24.
Muller S, Brun S, René F, de Sèze J, Loeffler JP, Jeltsch-David H. Autophagy in neuroinflammatory diseases. Autoimmun Rev 2017; S1568-9972: 30139-8.
Rouleau M, Patel A, Hendzel MJ, Kaufmann SH, Poirier GG. PARP inhibition: PARP1 and beyond. Nat Rev Cancer 2010; 10: 293-301.
Mangerich A, Bürkle A. Pleiotropic cellular functions of PARP1 in longevity and aging: genome maintenance meets inflammation. Oxid Med Cell Longev 2012; 2012: 321653.
Schiewer MJ, Knudsen KE. Transcriptional roles of PARP1 in cancer. Mol Cancer Res 2014; 12: 1069-80.
Beck C, Robert I, Reina-San-Martin B, Schreiber V, Dantzer F. Poly(ADP-ribose) polymerases in double-strand break repair: focus on PARP1, PARP2 and PARP3. Exp Cell Res 2014; 329: 18-25.
Malyuchenko NV, Kotova EY, Kulaeva OI, Kirpichnikov MP, Studitskiy VM. PARP1 Inhibitors: antitumor drug design. Acta Naturae, 2015; 7: 27-37.
Singh SS, Sarma JA, Narasu L, Dayam R, Xu S, Neamati N. A review on PARP1 inhibitors: Pharmacophore modeling, virtual and biological screening studies to identify novel PARP1 inhibitors. Curr Top Med Chem 2014; 14: 2020-30.
Mangerich A, Burkle A. Pleiotropic cellular functions of PARP1 in longevity and aging: genome maintenance meets inflammation. Oxid Med Cell Longev 2012; 2012: 321653.
Kwon DY, Han GH, Ulak R, Ki KD, Lee JM, Lee SK. Syndrome of inappropriate antidiuretic hormone secretion following irinotecan-cisplatin administration as a treatment for recurrent ovarian clear cell carcinoma. Obstet Gynecol Sci 2017; 60: 115-7.
Samuel P, Pink RC, Brooks SA, Carter DR. miRNAs and ovarian cancer: a miRiad of mechanisms to induce cisplatin drug resistance. Expert Rev Anticancer Ther 2016; 16: 57-70.
Park SH, Park HS, Lee JH, et al. Induction of endoplasmic reticulum stress-mediated apoptosis and non-canonical autophagy by luteolin in NCI-H460 lung carcinoma cells. Food Chem Toxicol 2013; 56: 100-9.
Peng M, Watanabe S, Chan KWK, et al. Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin. Antiviral Res 2017; 143: 176-185.
Wang Q, Wang H, Jia Y, Pan H, Ding H. Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma. Cancer Chemother Pharmacol 2017; 79: 1031-
Yan M, Liu Z, Yang H, et al. Luteolin decreases the UVA induced autophagy of human skin fibroblasts by scavenging ROS. Mol Med Rep 2016; 14: 1986-92.
Ji Y, Tulin AV. The roles of PARP1 in gene control and cell differentiation. Curr Opin Genet Dev 2010; 20: 512-8.