Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells
Skin cancer has high rates of mortality and therapeutic failure. In this study, to develop a multi-agent strategy for skin cancer management, the selective cytotoxicity of several alkaloid fractions and pure alkaloids isolated from Amaryllidaceae species was evaluated in melanoma cells. In addition,...
- Autores:
-
Castañeda, Carol
Bravo, Karent
Cortés, Natalie
Bedoya, Janeth
Borges, Warley de S.
Bastida, Jaume
Osorio, Edison
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2023
- Institución:
- Universidad de Ibagué
- Repositorio:
- Repositorio Universidad de Ibagué
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.unibague.edu.co:20.500.12313/3880
- Acceso en línea:
- https://hdl.handle.net/20.500.12313/3880
- Palabra clave:
- Amaryllidaceae alkaloids
Eucharis caucana
Photoprotection
Skin cancer
Zephyranthes carinata
- Rights
- openAccess
- License
- http://purl.org/coar/access_right/c_abf2
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dc.title.eng.fl_str_mv |
Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells |
title |
Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells |
spellingShingle |
Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells Amaryllidaceae alkaloids Eucharis caucana Photoprotection Skin cancer Zephyranthes carinata |
title_short |
Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells |
title_full |
Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells |
title_fullStr |
Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells |
title_full_unstemmed |
Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells |
title_sort |
Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells |
dc.creator.fl_str_mv |
Castañeda, Carol Bravo, Karent Cortés, Natalie Bedoya, Janeth Borges, Warley de S. Bastida, Jaume Osorio, Edison |
dc.contributor.author.none.fl_str_mv |
Castañeda, Carol Bravo, Karent Cortés, Natalie Bedoya, Janeth Borges, Warley de S. Bastida, Jaume Osorio, Edison |
dc.subject.proposal.eng.fl_str_mv |
Amaryllidaceae alkaloids Eucharis caucana Photoprotection Skin cancer Zephyranthes carinata |
topic |
Amaryllidaceae alkaloids Eucharis caucana Photoprotection Skin cancer Zephyranthes carinata |
description |
Skin cancer has high rates of mortality and therapeutic failure. In this study, to develop a multi-agent strategy for skin cancer management, the selective cytotoxicity of several alkaloid fractions and pure alkaloids isolated from Amaryllidaceae species was evaluated in melanoma cells. In addition, UVB-stimulated keratinocytes (HaCaT) were exposed to seven alkaloid fractions characterized by GC-MS, and the production of intracellular reactive oxygen species (ROS) and IL-6, were measured to evaluate their photoprotection effects. The Eucharis caucana (bulb) alkaloid fraction (20 μg/ml) had a clear effect on the viability of melanoma cells, reducing it by 45.7% without affecting healthy keratinocytes. This alkaloid fraction and tazettine (both at 2.5 μg/ml) suppressed UVB-induced ROS production by 31.6% and 29.4%, respectively. The highest anti-inflammatory potential was shown by the Zephyranthes carinata (bulb) alkaloid fraction (10 μg/ml), which reduced IL-6 production by 90.8%. According to the chemometric analysis, lycoramine and tazettine had a photoprotective effect on the UVB-exposed HaCaT cells, attenuating the production of ROS and IL-6. These results suggest that Amaryllidaceae alkaloids have photoprotective and therapeutic potential in skin cancer management, especially at low concentrations. |
publishDate |
2023 |
dc.date.accessioned.none.fl_str_mv |
2023-10-27T14:30:07Z |
dc.date.available.none.fl_str_mv |
2023-10-27T14:30:07Z |
dc.date.issued.none.fl_str_mv |
2023-03-31 |
dc.type.none.fl_str_mv |
Artículo de revista |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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http://purl.org/coar/resource_type/c_6501 |
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Castañeda C, Bravo K, Cortés N, Bedoya J, de Borges WS, Bastida J, Osorio E. Alcaloides de Amaryllidaceae en el manejo del cáncer de piel: efecto fotoprotector sobre queratinocitos humanos y actividad antiproliferativa en células de melanoma. J Appl Biomed. 2023;21(1):36-47. doi: 10.32725/jab.2023.004. PMID de PubMed: 37016777. |
dc.identifier.issn.none.fl_str_mv |
1214-021X |
dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/20.500.12313/3880 |
identifier_str_mv |
Castañeda C, Bravo K, Cortés N, Bedoya J, de Borges WS, Bastida J, Osorio E. Alcaloides de Amaryllidaceae en el manejo del cáncer de piel: efecto fotoprotector sobre queratinocitos humanos y actividad antiproliferativa en células de melanoma. J Appl Biomed. 2023;21(1):36-47. doi: 10.32725/jab.2023.004. PMID de PubMed: 37016777. 1214-021X |
url |
https://hdl.handle.net/20.500.12313/3880 |
dc.language.iso.none.fl_str_mv |
eng |
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eng |
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47 |
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1 |
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21 |
dc.relation.ispartofjournal.none.fl_str_mv |
Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells |
dc.relation.references.none.fl_str_mv |
Afaq F (2011). Natural agents: Cellular and molecular mechanisms of photoprotection. Arch Biochem Biophys 508(2): 144–151. DOI: 10.1016/j.abb.2010.12.007 Apalla Z, Lallas A, Sotiriou E, Lazaridou E, Ioannides D (2017b). Epidemiological trends in skin cancer. Dermatol Pract Concept 7(2): 1–6. DOI: 10.5826/dpc.0702a01 Apalla Z, Nashan D, Weller RB, Castellsagué X (2017a). Skin cancer: Epidemiology, disease burden, pathophysiology, diagnosis, and therapeutic approaches. Dermatol Ther (Heidelb) 7(Suppl. 1): 5–19. DOI: 10.1007/s13555-016-0165-y Atanasov AG, Zotchev SB, Dirsch VM, International Natural Product Sciences Taskforce, Supuran CT (2021). Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov 20(3): 200–216. DOI: 10.1038/s41573-020-00114-z. Bastida J, Lavilla R, Viladomat F (2006). Chapter 3 Chemical and Biological Aspects of Narcissus Alkaloids. Alkaloids Chem Biol 63: 87–179. DOI: 10.1016/s1099-4831(06)63003-4 Berkov S, Osorio E, Viladomat F, Bastida J (2020). Chemodiversity, chemotaxonomy and chemoecology of Amaryllidaceae alkaloids. Alkaloids Chem Biol 83: 113–185. DOI: 10.1016/ bs.alkal.2019.10.002 Bessa CDPB, de Andrade JP, de Oliveira RS, Domingos E, Santos H, Romão W, et al. (2017). Identification of alkaloids from Hippeastrum aulicum (Ker Gawl.) Herb. (Amaryllidaceae) using CGC-MS and ambient ionization mass spectrometry (PS-MS and LS-MS). J Braz Chem Soc 28(5): 819–830. DOI: 10.21577/0103- 5053.20160234 Bhatt VR, Shostrom V, Holstein SA, Al-Kadhimi ZS, Maness LJ, Berger A, et al. (2020). Survival of older adults with newly diagnosed acute myeloid leukemia: Effect of using multiagent versus single-agent chemotherapy. Clin Lymphoma Myeloma Leuk 20(5): e239–e258. DOI: 10.1016/j.clml.2020.01.015 Biswas SK (2016). Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox?. Oxid Med Cell Longev 2016: 5698931. DOI: 10.1155/2016/5698931 Bolton NM, Maerz AH, Brown RE, Bansal M, Bolton JS, Conway WC (2019). Multiagent neoadjuvant chemotherapy and tumor response are associated with improved survival in pancreatic cancer. Hpb (Oxford) 21(4): 413–418. DOI: 10.1016/j. hpb.2018.08.013 Cao Z, Yu D, Fu S, Zhang G, Pan Y, Bao M, et al. (2013). Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity. Toxicol Lett 218(2): 174–185. DOI: 10.1016/j.toxlet.2013.01.018 Chorachoo J, Saeloh D, Srichana T, Amnuaikit T, Musthafa KS, Sretrirutchai S, Voravuthikunchai SP (2016). Rhodomyrtone as a potential anti-proliferative and apoptosis inducing agent in HaCaT keratinocyte cells. Eur J Pharmacol 772: 144–151. DOI: 10.1016/j. ejphar.2015.12.005 Cortes N, Castañeda C, Osorio EH, Cardona-Gomez GP, Osorio E (2018). Amaryllidaceae alkaloids as agents with protective effects against oxidative neural cell injury. Life Sci 203: 54–65. DOI: 10.1016/j.lfs.2018.04.026 Cragg GM, Pezzuto JM (2016). Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med Princ Pract 25(Suppl. 2): 41–59. DOI: 10.1159/000443404 Cunningham JJ, Gatenby RA, Brown JS (2011). Evolutionary dynamics in cancer therapy. Mol Pharm 8(6): 2094–2100. DOI: 10.1021/mp2002279 Dasari R, Banuls LMY, Masi M, Pelly SC, Mathieu V, Green IR, et al. (2014). C1,C2-ether derivatives of the Amaryllidaceae alkaloid lycorine: Retention of activity of highly lipophilic analogues against cancer cells. Bioorganic Med Chem Lett 24(3): 923–927. DOI: 10.1016/j.bmcl.2013.12.073. Duque L, Bravo K, Osorio E (2017). A holistic anti-aging approach applied in selected cultivated medicinal plants: A view of photoprotection of the skin by different mechanisms. Ind Crops Prod 97: 431–439. DOI: 10.1016/j.indcrop.2016.12.059. Gordon R (2013). Skin cancer: An overview of epidemiology and risk factors. Semin Oncol Nurs 29(3): 160–169. DOI: 10.1016/j. soncn.2013.06.002 Gonring-Salarini K, Conti R, de Andrade JP, Borges BJ, Aguiar AC, de Souza J, et al. (2019). In vitro antiplasmodial activities of alkaloids isolated from roots of Worsleya procera (Lem.) Traub (Amaryllidaceae). J Braz Chem Soc 30(8): 51–58. DOI: 10.21577/0103-5053.20190061 Howes MJR (2018). The evolution of anticancer drug discovery from plants. Lancet Oncol 19(3): 293–294. DOI: 10.1016/S1470- 2045(18)30136-0. Ingrassia L, Lefranc F, Dewelle J, Pottier L, Mathieu V, SpieglKreinecker S, et al. (2009). Structure-activity relationship analysis of novel derivatives of narciclasine (an Amaryllidaceae isocarbostyril derivative) as potential anticancer agents. J Med Chem 52(4): 1100–1114. DOI: 10.1021/jm8013585 Kornienko A, Evidente A (2008). Chemistry, biology, and medicinal potential of narciclasine and its congeners. Chem Rev 108(6): 1982–2014. DOI: 10.1021/cr078198u Kozma B, Eide MJ (2014). Photocarcinogenesis: An epidemiologic perspective on ultraviolet light and skin cancer. Dermatol Clin 32(3): 301–313. DOI: 10.1016/j.det.2014.03.004 Kucheryavskiy S (2021). Getting started with mdatools for R. [online] [cit. 2021-11-20]. Available from: https://mdatools.com/ docs/ Lee JH, An HT, Chung JH, Kim KH, Eun HC, Cho KC (2002). Acute effects of UVB radiation on the proliferation and differentiation of keratinocytes. Photodermatol Photoimmunol Photomed 18(5): 253–261. DOI: 10.1034/j.1600-0781.2002.02755.x Lee WR, Lin YK, Alalaiwe A, Wang PW, Liu PY, Fang JY (2020). Fractional laser-mediated siRNA delivery for mitigating psoriasislike lesions via IL-6 silencing. Mol Ther Nucleic Acids 19: 240–251. DOI: 10.1016/j.omtn.2019.11.013 Lianza M, Verdan MH, de Andrade JP, Poli F, de Almeida LC, Costa-Lotufo LV, et al. (2020). Isolation, absolute configuration and cytotoxic activities of alkaloids from Hippeastrum goianum (Ravenna) Meerow (Amaryllidaceae). J Braz Chem Soc 31: 2135–2145. DOI: 10.21577/0103-5053.20200116 Lu JJ, Wang YT (2020). Identification of anti-cancer compounds from natural products. Chin J Nat Med 18(7): 481–482. DOI: 10.1016/S1875-5364(20)30057-1. Maier MJ (2015). Package ‘REdaS’. [online] [cit. 2021-11-20]. Available from: https://cran.r-project.org/web/packages/REdaS/ REdaS.pdf Masi M, Van Slambrouck S, Gunawardana S, van Rensburg MJ, James PC, Mochel JG, et al. (2019). Alkaloids isolated from Haemanthus humilis Jacq., an indigenous South African Amaryllidaceae: Anticancer activity of coccinine and montanine. South African J Bot 126: 277–281. DOI: 10.1016/j. sajb.2019.01.036. Mevik BH, Wehrens R, Liland KH, Hiemstra P (2019). Package ‘pls’: Partial least squares and principal component regression. [online] [cit. 2021-11-20]. Available from: https://github.com/bhmevik/pls Montes de Oca MK, Pearlman RL, McClees SF, Strickland R, Afaq F (2017). Phytochemicals for the prevention of photocarcinogenesis. Photochem Photobiol 93(4): 956–974. DOI: 10.1111/php.12711 Muramatsu S, Kubo R, Nishida E, Shintani Y, Morita A (2016). Serum interleukin-6 levels in response to biologic treatment in patients with psoriasis. Mod Rheumatol 27(1): 137–141. DOI: 10.3109/14397595.2016.1174328 Nair JJ, Bastida J, van Staden J (2016b). In vivo cytotoxicity studies of Amaryllidaceae alkaloids. Nat Prod Commun 11(1): 121–132 Nair JJ, Bastida J, Viladomat F, van Staden J (2012). Cytotoxic agents of the crinane series of Amaryllidaceae alkaloids. Nat Prod Commun 7(12): 1677–1688 Nair JJ, van Staden J, Bastida J (2016a). Cytotoxic alkaloid constituents of the Amaryllidaceae. Stud Nat Prod Chem 49: 107–156. DOI: 10.1016/B978-0-444-63601-0.00003-X. Newman DJ, Cragg GM (2020). Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod 83(3): 770–803. DOI: 10.1021/acs.jnatprod.9b01285 Nichols JA, Katiyar SK (2010). Skin photoprotection by natural polyphenols: Anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res 302(2): 71–83. DOI: 10.1007/ s00403-009-1001-3 Nieweg OE, Gallegos-Hernández JF (2016). Cutaneous melanoma and the new drugs. Cir Cir (English Ed) 83(2): 175–180. DOI: 10.1016/j.circen.2015.08.016 Oak ASW, Athar M, Yusuf N, Elmets CA (2018). UV and Skin: Photocarcinogenesis. In: Environment and Skin. Switzerland: Springer International Publishing. pp. 67–103. DOI: 10.1007/978- 3-319-43102-4_8 Qiao P, Guo W, Ke Y, Fang H, Zhuang Y, Jiang M, et al. (2019). Mechanical stretch exacerbates psoriasis by stimulating keratinocyte proliferation and cytokine production. J Invest Dermatol 139(7): 1470–1479. DOI: 10.1016/j.jid.2018.12.019 Qiu S, Sun H, Zhang AH, Xu HY, Yan GL, Han Y, Wang XJ (2014). Natural alkaloids: Basic aspects, biological roles, and future perspectives. Chin J Nat Med 12(6): 401–406. DOI: 10.1016/ S1875-5364(14)60063-7 Real FX, López C (2016). Medicina Interna. Madrid: Elsevier, pp. 1191–1202. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010). Oxidative stress, inflammation, and cancer: How are they linked? Exp Ther 49(11): 1603–1616. DOI: 10.1016/j.freeradbiomed.2010.09.006. Roussi F, Gueritte F, Fahy J (2012). The vinca alkaloids. In: Cragg GM, Kingston DGI, Newman DJ (Eds). Anticancer agents from natural products. Second ed. CRC/Taylor & Francis, Boca Raton, pp. 177–198 Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancer in 185 countries. CA Cancer J Clin 71(3): 209–249. DOI: 10.3322/ caac.21660. Traykova M, Traykov T, Hadjimitova V, Krikorian K, Bojadgieva N (2003). Antioxidant properties of galantamine hydrobromide. Z Naturforsch C J Biosci 58(5–6): 361–365. DOI: 10.1515/znc2003-5-613 Voiculescu VM, Lisievici CV, Lupu M, Vajaitu C, Draghici CC, Popa AV, et al. (2019). Mediators of inflammation in topical therapy of skin cancers. Mediators Inflamm 2019: 8369690. DOI: 10.1155/2019/8369690. Wang C, Wang Q, Li X, Jin Z, Xu P, Xu N, et al. (2016). Lycorine induces apoptosis of bladder cancer T24 cells by inhibiting phospho-Akt and activating the intrinsic apoptotic cascade. Biochem Biophys Res Commun 483(1): 197–202. DOI: 10.1016/j. bbrc.2016.12.168 Wu D, Yotnda P (2011). Production and detection of reactive oxygen species (ROS) in cancers. J Vis Exp (57): e3357. DOI: 10.3791/3357 Ying X, Huang A, Xing Y, Lan L, Yi Z, He P (2017). Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway. Sci China Life Sci 60(4): 417–428. DOI: 10.1007/s11427-016-0368-y |
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Castañeda, Carol28ad4e9a-ea70-476d-8f1c-6c6717d71b37-1Bravo, Karent9063b3a7-cacb-4333-82b9-0f428f60f38e-1Cortés, Natalie16e73ae2-5c91-425c-9ce1-5026766280f8-1Bedoya, Janeth82bfd55c-e000-4b86-b5e0-e6d35cc01c8a-1Borges, Warley de S.bc1bffcc-97a6-4239-88c2-a10923de17ae-1Bastida, Jaume00ea29d6-11a2-48bd-bc9e-2dd48a2bc06e-1Osorio, Edisone6d834e4-46ca-40f0-ab7c-630a35856901-12023-10-27T14:30:07Z2023-10-27T14:30:07Z2023-03-31Skin cancer has high rates of mortality and therapeutic failure. In this study, to develop a multi-agent strategy for skin cancer management, the selective cytotoxicity of several alkaloid fractions and pure alkaloids isolated from Amaryllidaceae species was evaluated in melanoma cells. In addition, UVB-stimulated keratinocytes (HaCaT) were exposed to seven alkaloid fractions characterized by GC-MS, and the production of intracellular reactive oxygen species (ROS) and IL-6, were measured to evaluate their photoprotection effects. The Eucharis caucana (bulb) alkaloid fraction (20 μg/ml) had a clear effect on the viability of melanoma cells, reducing it by 45.7% without affecting healthy keratinocytes. This alkaloid fraction and tazettine (both at 2.5 μg/ml) suppressed UVB-induced ROS production by 31.6% and 29.4%, respectively. The highest anti-inflammatory potential was shown by the Zephyranthes carinata (bulb) alkaloid fraction (10 μg/ml), which reduced IL-6 production by 90.8%. According to the chemometric analysis, lycoramine and tazettine had a photoprotective effect on the UVB-exposed HaCaT cells, attenuating the production of ROS and IL-6. These results suggest that Amaryllidaceae alkaloids have photoprotective and therapeutic potential in skin cancer management, especially at low concentrations.12 páginasapplication/pdfCastañeda C, Bravo K, Cortés N, Bedoya J, de Borges WS, Bastida J, Osorio E. Alcaloides de Amaryllidaceae en el manejo del cáncer de piel: efecto fotoprotector sobre queratinocitos humanos y actividad antiproliferativa en células de melanoma. J Appl Biomed. 2023;21(1):36-47. doi: 10.32725/jab.2023.004. PMID de PubMed: 37016777.1214-021Xhttps://hdl.handle.net/20.500.12313/3880engRepublica Checa4713621Amaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cellsAfaq F (2011). Natural agents: Cellular and molecular mechanisms of photoprotection. Arch Biochem Biophys 508(2): 144–151. DOI: 10.1016/j.abb.2010.12.007Apalla Z, Lallas A, Sotiriou E, Lazaridou E, Ioannides D (2017b). Epidemiological trends in skin cancer. Dermatol Pract Concept 7(2): 1–6. DOI: 10.5826/dpc.0702a01Apalla Z, Nashan D, Weller RB, Castellsagué X (2017a). Skin cancer: Epidemiology, disease burden, pathophysiology, diagnosis, and therapeutic approaches. Dermatol Ther (Heidelb) 7(Suppl. 1): 5–19. DOI: 10.1007/s13555-016-0165-yAtanasov AG, Zotchev SB, Dirsch VM, International Natural Product Sciences Taskforce, Supuran CT (2021). Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov 20(3): 200–216. DOI: 10.1038/s41573-020-00114-z.Bastida J, Lavilla R, Viladomat F (2006). Chapter 3 Chemical and Biological Aspects of Narcissus Alkaloids. Alkaloids Chem Biol 63: 87–179. DOI: 10.1016/s1099-4831(06)63003-4Berkov S, Osorio E, Viladomat F, Bastida J (2020). Chemodiversity, chemotaxonomy and chemoecology of Amaryllidaceae alkaloids. Alkaloids Chem Biol 83: 113–185. DOI: 10.1016/ bs.alkal.2019.10.002Bessa CDPB, de Andrade JP, de Oliveira RS, Domingos E, Santos H, Romão W, et al. (2017). Identification of alkaloids from Hippeastrum aulicum (Ker Gawl.) Herb. (Amaryllidaceae) using CGC-MS and ambient ionization mass spectrometry (PS-MS and LS-MS). J Braz Chem Soc 28(5): 819–830. DOI: 10.21577/0103- 5053.20160234Bhatt VR, Shostrom V, Holstein SA, Al-Kadhimi ZS, Maness LJ, Berger A, et al. (2020). Survival of older adults with newly diagnosed acute myeloid leukemia: Effect of using multiagent versus single-agent chemotherapy. Clin Lymphoma Myeloma Leuk 20(5): e239–e258. DOI: 10.1016/j.clml.2020.01.015Biswas SK (2016). Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox?. Oxid Med Cell Longev 2016: 5698931. DOI: 10.1155/2016/5698931Bolton NM, Maerz AH, Brown RE, Bansal M, Bolton JS, Conway WC (2019). Multiagent neoadjuvant chemotherapy and tumor response are associated with improved survival in pancreatic cancer. Hpb (Oxford) 21(4): 413–418. DOI: 10.1016/j. hpb.2018.08.013Cao Z, Yu D, Fu S, Zhang G, Pan Y, Bao M, et al. (2013). Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity. Toxicol Lett 218(2): 174–185. 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