Curcumin Enhances the Anticancer Effects of Binimetinib on Melanoma Cells by Inducing Mitochondrial Dysfunction and Cell Apoptosis with Necroptosis
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Background: Recent studies suggest that MEK1/2 inhibitors, including binimetinib, signifi- cantly improve malignant melanoma (MM) patient survival. Growing evidence suggests that phytochemicals, especially curcumin, can overcome drug resistance in cancer cells through a variety of mechanisms. Objective: This study aims to examine curcumin’s efficacy in vitro combined with bin- imetinib in human MM cells. Methods: We used 2D monolayer and 3D spheroid human epidermal melanocyte culture models, HEMn-MP (human epidermal melanocytes, neonatal, moderately pigmented), and two human MM cell lines, G361 and SK-MEL-2, to evaluate cell viability, proliferation, mi- gration, death, and reactive oxygen species (ROS) production following single therapy treat- ment, with either curcumin or binimetinib, or a combination of both. Results: Compared to MM cells treated with single therapy, those with combination therapy showed significantly decreased cell viability and increased ROS production. We observed apoptosis following both single and combination therapies. However only those who had had combination therapy had necroptosis. Conclusion: Collectively, our data demonstrates that curcumin exerts significant synergistic anticancer effects on MM cells by inducing ROS and necroptosis when combined with bin- imetinib. Therefore, a strategy of adding curcumin to conventional anticancer agents holds promise for treating MM.
Abstract
Background: Recent studies suggest that MEK1/2 inhibitors, including binimetinib, signifi- cantly improve malignant melanoma (MM) patient survival. Growing evidence suggests that phytochemicals, especially curcumin, can overcome drug resistance in cancer cells through a variety of mechanisms. Objective: This study aims to examine curcumin’s efficacy in vitro combined with bin- imetinib in human MM cells. Methods: We used 2D monolayer and 3D spheroid human epidermal melanocyte culture models, HEMn-MP (human epidermal melanocytes, neonatal, moderately pigmented), and two human MM cell lines, G361 and SK-MEL-2, to evaluate cell viability, proliferation, mi- gration, death, and reactive oxygen species (ROS) production following single therapy treat- ment, with either curcumin or binimetinib, or a combination of both. Results: Compared to MM cells treated with single therapy, those with combination therapy showed significantly decreased cell viability and increased ROS production. We observed apoptosis following both single and combination therapies. However only those who had had combination therapy had necroptosis. Conclusion: Collectively, our data demonstrates that curcumin exerts significant synergistic anticancer effects on MM cells by inducing ROS and necroptosis when combined with bin- imetinib. Therefore, a strategy of adding curcumin to conventional anticancer agents holds promise for treating MM.
참고문헌 (51)
- Sladden MJ, "Surgical excision margins for primary cutaneous melanoma", Cochrane Database Syst Rev, (4), pp.CD004835~ (2009)
- Siegel RL, "Cancer statistics, 2022", CA Cancer J Clin, 72, pp.7~33 (2022)
- "Cancer stat facts: melanoma of the skin" (2022)[URL]
- Carole Yolande Perrot, "Insights into the Transforming Growth Factor-β Signaling Pathway in Cutaneous Melanoma", Annals of Dermatology, 25(2), pp.135~144 (2013), 대한피부과학회
- 홍진우, "Prognostic and Clinicopathologic Associations of BRAF Mutation in Primary Acral Lentiginous Melanoma in Korean Patients: A Preliminary Study", Annals of Dermatology, 26(2), pp.195~202 (2014), 대한피부과학회
- Long GV, "COMBI-d : a randomized, double-blinded, Phase III study comparing the combination of dabrafenib and trametinib to dabrafenib and trametinib placebo as first-line therapy in patients(pts)with unresectable or metastatic BRAFV600E", K mutation-positive cutaneous melanoma, 2014, pp.32(15 Suppl), 9011~
- Larkin J, "Combined vemurafenib and cobimetinib in BRAF-mutated melanoma", N Engl J Med, 371, pp.1867~1876 (2014)
- Dummer R, "Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib(COLUMBUS) : a multicentre, open-label, randomised, phase 3 trial", Lancet Oncol, 19, pp.1315~1327 (2018)
- Grob JJ, "Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on healthrelated quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma(COMBIv) : results of a phase 3, open-label, randomised trial", Lancet Oncol, 16, pp.1389~1398 (2015)
- Long GV, "Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma who received dabrafenib combined with trametinib", J Clin Oncol, 36, pp.667~673 (2018)
- Tinoush B, "Phytochemicals : potential lead molecules for MDR reversal", Front Pharmacol, 11, pp.832~ (2020)
- Keyvani-Ghamsari S, "Curcumin effect on cancer cells' multidrug resistance : an update", Phytother Res, 34, pp.2534~2556 (2020)
- Chiu YJ, "Curcumin suppresses cell proliferation and triggers apoptosis in vemurafenib-resistant melanoma cells by downregulating the EGFR signaling pathway", Environ Toxicol, 37, pp.868~879 (2022)
- Lee YJ, "Arctigenin induces necroptosis through mitochondrial dysfunction with CCN1 upregulation in prostate cancer cells under lactic acidosis", Mol Cell Biochem, 467, pp.45~56 (2020)
- Chambers KF, "3D Cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer", PLoS One, 9, pp.e111029~ (2014)
- Liu RH, "Potential synergy of phytochemicals in cancer prevention : mechanism of action", J Nutr, 134(12 Suppl), pp.3479~ (2004)
- Khan F, "Comprehensive review on phytochemicals, pharmacological and clinical potentials of Gymnema sylvestre", Front Pharmacol, 10, pp.1223~ (2019)
- 이상훈, "Screening of Plant-Derived Natural Extracts to Identify a Candidate Extract Capable of Enhancing Lipid Synthesis in Keratinocytes", Annals of Dermatology, 34(5), pp.331~339 (2022), 대한피부과학회[DOI]
- Zhang YP, "Effect of curcumin on the proliferation, apoptosis, migration, and invasion of human melanoma A375 cells", Genet Mol Res, 14, pp.1056~1067 (2015)
- Philip S, "Osteopontin induces nuclear factor kappa Bmediated promatrix metalloproteinase-2 activation through I kappa B alpha", IKK signaling pathways, and curcumin(diferulolylmethane)down-regulates these pathways, 2003, pp.278, 14487~14497
- Jiang AJ, "Curcumin induces apoptosis through mitochondrial pathway and caspases activation in human melanoma cells", Mol Biol Rep, 42, pp.267~275 (2015)
- Oelkrug C, "Analysis of the tumoricidal and anti-cachectic potential of curcumin", Anticancer Res, 34, pp.4781~4788 (2014)
- Buss S, "Visible light is a better co-inducer of apoptosis for curcumin-treated human melanoma cells than UVA", PLoS One, 8, pp.e79748~ (2013)
- Tu CX, "Curcumin inhibits melanogenesis in human melanocytes", Phytother Res, 26, pp.174~179 (2012)
- Purkayastha S, "Curcumin blocks brain tumor formation", Brain Res, 1266, pp.130~138 (2009)
- 이윤주, "Involvement of ROS in Curcumin-induced Autophagic Cell Death", The Korean Journal of Physiology & Pharmacology, 15(1), pp.1~7 (2011), 대한약리학회
- Lee YJ, "Curcumin targets both apoptosis and necroptosis in acidity-tolerant prostate carcinoma cells", Biomed Res Int, 2021, pp.8859181~ (2021)
- Cao X, "Curcumin suppresses tumorigenesis by ferroptosis in breast cancer", PLoS One, 17, pp.e0261370~ (2022)
- Dhuriya YK, "Necroptosis : a regulated inflammatory mode of cell death", J Neuroinflammation, 15, pp.199~ (2018)
- Ando Y, "Necroptosis in pancreatic cancer promotes cancer cell migration and invasion by release of CXCL5", PLoS One, 15, pp.e0228015~ (2020)
- Shen F, "Pharmacological inhibition of necroptosis promotes human breast cancer cell proliferation and metastasis", Onco Targets Ther, 13, pp.3165~3176 (2020)
- Park JE, "Expression of key regulatory genes in necroptosis and its effect on the prognosis in non-small cell lung cancer", J Cancer, 11, pp.5503~5510 (2020)
- Wang Q, "RIP1 potentiates BPDE-induced transformation in human bronchial epithelial cells through catalase-mediated suppression of excessive reactive oxygen species", Carcinogenesis, 34, pp.2119~2128 (2013)
- Geserick P, "Absence of RIPK3 predicts necroptosis resistance in malignant melanoma", Cell Death Dis, 6, pp.e1884~ (2015)
- Bozec D, "Critical function of the necroptosis adaptor RIPK3 in protecting from intestinal tumorigenesis", Oncotarget, 7, pp.46384~46400 (2016)
- Espinosa-Diez C, "Antioxidant responses and cellular adjustments to oxidative stress", Redox Biol, 6, pp.183~197 (2015)
- 곽미희, "Dieckol Inhibits the Effects of Particulate Matter 10 on Sebocytes, Outer Root Sheath Cells, and Cutibacterium Acnes−Pretreated Mice", Annals of Dermatology, 34(3), pp.182~190 (2022), 대한피부과학회[DOI]
- Cesi G, "ROS production induced by BRAF inhibitor treatment rewires metabolic processes affecting cell growth of melanoma cells", Mol Cancer, 16, pp.102~ (2017)
- Yuan L, "BRAF mutant melanoma adjusts to BRAF", MEK inhibitors via dependence on increased antioxidant SOD2 and increased reactive oxygen species levels, 2020, pp.12, 1661~
- Pizzimenti S, "Oxidative stress-related mechanisms in melanoma and in the acquired resistance to targeted therapies", Antioxidants(Basel), 10, pp.1942~ (2021)
- Redza-Dutordoir M, "Activation of apoptosis signalling pathways by reactive oxygen species", Biochim Biophys Acta, 1863, pp.2977~2992 (2016)
- Baker A, "Redox control of caspase-3 activity by thioredoxin and other reduced proteins", Biochem Biophys Res Commun, 268, pp.78~81 (2000)
- Braunstein I, "Opposing effects of polysulfides and thioredoxin on apoptosis through caspase persulfidation", J Biol Chem, 295, pp.3590~3600 (2020)
- Benhar M, "Oxidants, antioxidants and thiol redox switches in the control of regulated cell death pathways", Antioxidants(Basel), 9, pp.309~ (2020)
- Yoon‑Jin Lee, "Apoptosis and necroptosis‑inducing effects of arctigenin on nasal septum carcinoma RPMI‑2650 cells in 2D and 3D culture", Molecular & Cellular Toxicology, 16(1), pp.1~11 (2020), 대한독성 유전단백체 학회
- Cheng AL, "Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions", Anticancer Res, 21, pp.2895~2900 (2001)
- Tabanelli R, "Improving curcumin bioavailability : current strategies and future perspectives", Pharmaceutics, 13, pp.1715~ (2021)
- Wang B, "Improving antimelanoma effect of curcumin by biodegradable nanoparticles", Oncotarget, 8, pp.108624~108642 (2017)
- Mardani R, "Nanomicellar-curcumin exerts its therapeutic effects via affecting angiogenesis, apoptosis, and T cells in a mouse model of melanoma lung metastasis", Pathol Res Pract, 216, pp.153082~ (2020)
- Jensen C, "Is It time to start transitioning from 2D to 3D cell culture?", Front Mol Biosci, 7, pp.33~ (2020)
- Lee JM, "A three-dimensional microenvironment alters protein expression and chemosensitivity of epithelial ovarian cancer cells in vitro", Lab Invest, 93, pp.528~542 (2013)