Chiết xuất từ quả Elaeocarpus reticulatus làm giảm khả năng sống sót và kích thích quá trình apoptosis trên các tế bào ung thư tụy trong ống nghiệm

Springer Science and Business Media LLC - Tập 47 - Trang 2073-2084 - 2020
Alexandria Turner1, Danielle R. Bond1,2, Quan V. Vuong1, Anita Chalmers1, Emma L. Beckett1,2, Judith Weidenhofer2,3, Christopher J. Scarlett1
1School of Environmental and Life Sciences, University of Newcastle, Ourimbah, Australia
2Hunter Medical Research Institute, New Lambton Heights, Australia
3School of Biomedical Sciences and Pharmacy, University of Newcastle, Ourimbah, Australia

Tóm tắt

Các lựa chọn điều trị cho ung thư tụy (PC) bị giới hạn nghiêm trọng do chẩn đoán muộn, di căn sớm và sự không đầy đủ của hóa trị và xạ trị trong việc chống lại sinh học hung hãn của bệnh. Trong những năm gần đây, các hợp chất sinh học hoạt tính xuất phát từ thực vật đã nổi lên như một nguồn cung cấp các tác nhân chống ung thư mới. Được sử dụng trong y học truyền thống trên toàn thế giới, các loài Elaeocarpus đã được báo cáo có tính chất chống viêm, chống oxy hóa và chống ung thư. Nghiên cứu này nhằm mục đích phân lập và xác định các hợp chất tiềm năng chống ung thư tụy trong quả của Elaeocarpus reticulatus Sm. Một chiết xuất thô acetone 50% đã làm giảm đáng kể khả năng sống sót của bốn dòng tế bào tụy (≥ 10 µg/mL cho các tế bào BxPC-3) và kích thích quá trình apoptosis ở các tế bào BxPC-3 và HPDE. Phân tích bằng HPLC đã xác định triterpenoid Cucurbitacin I là một thành phần có khả năng tồn tại trong chiết xuất. Hơn nữa, điều trị với Cucurbitacin I đã làm giảm đáng kể khả năng sống sót của các tế bào HPDE và BxPC-3, với kết quả so sánh được với cùng nồng độ của gemcitabine. Đáng chú ý, những nỗ lực để phân lập các hợp chất sinh học hoạt tính đã cho thấy rằng chiết xuất thô hiệu quả hơn trong việc giảm khả năng sống của tế bào PC so với các chiết xuất phân đoạn. Nghiên cứu này cung cấp những hiểu biết ban đầu về các thành phần sinh học hoạt tính của quả E. reticulatus.

Từ khóa

#ung thư tụy #Elaeocarpus reticulatus #Cucurbitacin I #apoptosis #tế bào BxPC-3

Tài liệu tham khảo

Siegel RL, Miller KD, Jemal A (2018) Cancer statistics. CA Cancer J Clin 68(1):7–30 Rawla P, Sunkara T, Gaduputi V (2019) Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol 10(1):10–27 Ilic M, Ilic I (2016) Epidemiology of pancreatic cancer. World J Gastroenterol 22(44):9694–9705 Falasca M, Kim M, Casari I (2016) Pancreatic cancer: current research and future directions. BBA Rev Cancer 1865:123–132 Hashimoto D et al (2016) Heterogeneity of KRAS mutations in pancreatic ductal adenocarcinoma. Pancreas 45(8):1111–1114 Verbeke C (2016) Morphological heterogeneity in ductal adenocarcinoma of the pancreas—does it matter? Pancreatology 16(3):295–301 Kleppe M, Levine RL (2014) Tumor heterogeneity confounds and illuminates: assessing the implications. Nat Med 20(4):342–344 Apaya MK, Chang MT, Shyur LF (2016) Phytomedicine polypharmacology: cancer therapy through modulating the tumor microenvironment and oxylipin dynamics. Pharmacol Ther 162:1–206 Apte MV et al (2013) A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology 144(6):1210–1219 Jiang J-H et al (2015) Epithelial–mesenchymal transition in pancreatic cancer: is it a clinically significant factor? BBA Rev Cancer 1855:43–49 Abel EV, Simeone DM (2013) Biology and clinical applications of pancreatic cancer stem cells. Gastroenterology 144(6):1241–1248 Li Y et al (2013) Pancreatic cancer stem cells: emerging target for designing novel therapy. Cancer Lett 338(1):94–100 Tang B et al (2016) Calcium sensing receptor suppresses human pancreatic tumorigenesis through a novel NCX1/Ca/beta-catenin signaling pathway. Cancer Lett 377(1):44–54 Jones S et al (2008) Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321(5897):1801–1806 Waddell N et al (2015) Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 518(7540):495–501 Dimou F et al (2015) Trends in receipt and timing of multimodality therapy in early-stage pancreatic cancer. J Gastrointest Surg 20(1):93–103 Conroy T et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. New Engl J Med 364(19):1817–1825 Chiorean EG, Coveler AL (2015) Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies. Drug Des Dev Ther 9:3529–3545 Iorio MV, Croce CM (2012) MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 4(3):143–159 Bhanot A, Sharma R, Noolvi MN (2011) Natural sources as potential anti-cancer agents: a review. Int J Phytomed 3(1):18 Tewari D, Rawat P, Singh PK (2019) Adverse drug reactions of anticancer drugs derived from natural sources. Food Chem Toxicol 123:522–535 Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75(3):311–335 Liu LF et al (2000) Mechanism of action of camptothecin. Ann N Y Acad Sci 922(1):1–10 Dumontet C, Jordan MA (2010) Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov 9(10):790–803 Vaccaro V et al (2015) Metastatic pancreatic cancer: is there a light at the end of the tunnel? World J Gastroenterol 21(16):4788–4801 Gardner ER et al (2008) Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Clin Cancer Res 14(13):4200–4205 Passacantilli I et al (2018) Co-treatment with gemcitabine and nab-paclitaxel exerts additive effects on pancreatic cancer cell death. Oncol Rep 39(4):1984–1990 Mohanty S, Cock IE (2012) The chemotherapeutic potential of Terminalia ferdinandiana: phytochemistry and bioactivity. Pharmacogn Rev 6(11):29–36 Vuong QV et al (2014) Fruit-derived phenolic compounds and pancreatic cancer: perspectives from Australian native fruits. J Ethnopharmacol 152(2):227–242 Pandey KB, Rizvi SI (2009) Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2(5):270–278 Rickard S (2011) The new ornamental garden. CSIRO Publishing Gardening Guides, Collingwood Vuong QV et al (2018) Fruit characteristics, phytochemical and antioxidant properties of blueberry ash (Elaeocarpus reticulatus). Heliyon 4(10):e00834 Michael JP (2016) Chapter one—Simple indolizidine and quinolizidine alkaloids. In: Hans-Joachim K (ed) The alkaloids: chemistry and biology. Academic Press, Cambridge, pp 1–498 Singh RK, Bhattacharya SK, Acharya SB (2000) Studies on extracts of Elaeocarpus sphaericus fruits on in vitro rat mast cells. Phytomedicine 7(3):205–207 Garg K, Goswami K, Khurana G (2013) A pharmacognostical review on Elaeocarpus sphaericus. Int J Pharm Pharm Sci 5:3–8 Utami R et al (2013) Phenolic contents, antioxidant and cytotoxic activities of Elaeocarpus floribundus Blume. Pak J Pharm Sci 26(2):245–250 Hule AK et al (2011) An evaluation of the antidiabetic effects of Elaeocarpus ganitrus in experimental animals. Indian J Pharmacol 43(1):56–59 Singh B et al (2015) Phytochemical and biological aspects of Rudraksha, the stony endocarp of Elaeocarpus ganitrus (Roxb.): a review. Isr J Plant Sci 62(4):1–11 Geetha DH, Rajeswari M, Jayashree I (2013) Chemical profiling of Elaeocarpus serratus L. by GC-MS. Asian Pac J Trop Biomed 3(12):985–987 Joshi S et al (2012) A comprehensive report on therapeutic potential of Elaeocarpus ganitrus Roxb.(Rudraksha). Environ Conserv J 13(3):147–150 Meng D et al (2008) Cytotoxic cucurbitane-type triterpenoids from Elaeocarpus hainanensis. Planta Med 74(14):1741–1744 Fang X et al (1984) Plant anticancer agents, XXXIV. Cucurbitacins from Elaeocarpus dolichostylus. J Nat Prod 47(6):988–993 Harden GJ (2005) Flora of New South Wales, Vol. 1. University of NSW Press, Royal Botanic Gardens Sydney, Sydney Ouyang H et al (2000) Immortal human pancreatic duct epithelial cell lines with near normal genotype and phenotype. Am J Pathol 157(5):1623–1631 Schoumacher RA et al (1990) A cystic fibrosis pancreatic adenocarcinoma cell line. Proc Natl Acad Sci USA 87(10):4012–4016 Tan MH et al (1986) Characterization of a new primary human pancreatic tumor line. Cancer Invest 4(1):15–23 Yunis AA, Arimura GK, Russin DJ (1977) Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: sensitivity to asparaginase. Int J Cancer 19(1):128–135 Do QD et al (2014) Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of Limnophila aromatica. J Food Drug Anal 22(3):296–302 Alothman M, Bhat R, Karim AA (2009) Antioxidant capacity and phenolic content of selected tropical fruits from Malaysia, extracted with different solvents. Food Chem 115(3):785–788 Dai J, Mumper RJ (2010) Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules 15(10):7313 Xuan TD et al (2007) Efficacy of extracting solvents to chemical components of kava (Piper methysticum) roots. J Nat Med 62(2):188 Symonds EL, Konczak I, Fenech M (2013) The Australian fruit Illawarra plum (Podocarpus elatus Endl., Podocarpaceae) inhibits telomerase, increases histone deacetylase activity and decreases proliferation of colon cancer cells. Br J Nutr 109(12):2117–2125 Tan AC et al (2011) Native Australian fruit polyphenols inhibit cell viability and induce apoptosis in human cancer cell lines. Nutr Cancer 63(3):444–455 Varughese B, Tripathi J (2013) Phytochemical evaluation of different solvent extracts of Aegle marmelos fruit at different stages of its ripening. Adv Life Sci Technol 8:8–12 Gami B (2016) Screening of methanol & acetone extract for antimicrobial activity of some medicinal plants species of Indian folklore. Int J Res Pharm Sci 2(1):69–75 Zhu ZX et al (2010) [Effects of gemcitabine and pemetrexed on the proliferation of pancreatic cancer cell lines BXPC-3 and PANC-1 in vitro]. Nan Fang Yi Ke Da Xue Xue Bao 30(1):149–152 Cappella P et al (2001) Cell cycle effects of gemcitabine. Int J Cancer 93(3):401–408 Habiro A et al (2004) Involvement of p38 mitogen-activated protein kinase in gemcitabine-induced apoptosis in human pancreatic cancer cells. Biochem Biophys Res Commun 316(1):71–77 de S Cavalcante, L. and Monteiro G (2014) Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol 741:8–16 Yong-Xian G et al (2016) Gemcitabine inhibits proliferation and induces apoptosis in human pancreatic cancer PANC-1 cells. J Cancer Res Ther 12(5):1–4 Hamed SS, Straubinger RM, Jusko WJ (2013) Pharmacodynamic modeling of cell cycle and apoptotic effects of gemcitabine on pancreatic adenocarcinoma cells. Cancer Chemother Pharmacol 72(3):553–563 Jaganathan R et al (2013) Potential therapeutic role of Tridham in human hepatocellular carcinoma cell line through induction of p53 independent apoptosis. BMC Complement Altern Med 13(1):323 Liu RH (2004) Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134(12):3479S-3485S Rasoanaivo P et al (2011) Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions. Malaria J 10(Suppl 1):S4–S4 Pan L et al (2012) Isolation, structure elucidation, and biological evaluation of 16,23-epoxycucurbitacin constituents from Eleaocarpus chinensis. J Nat Prod 75(3):444–452 Ito A et al (2002) Ellagic acid derivatives and cytotoxic cucurbitacins from Elaeocarpus mastersii. Phytochemistry 61(2):171–174 Alghasham AA (2013) Cucurbitacins—a promising target for cancer therapy. Int J Health Sci 7(1):77–89 Zhang Z-R, Gao M-X, Yang K (2017) Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways. Exp Ther Med 14(1):805–812 Sikander M et al (2016) Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer. Sci Rep 6:36594 Blaskovich MA et al (2003) Discovery of JSI-124 (Cucurbitacin I), a selective janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res 63(6):1270–1279 Qi J et al (2015) JSI-124 (Cucurbitacin I) inhibits tumor angiogenesis of human breast cancer through reduction of STAT3 phosphorylation. Am J Chin Med 43(2):337–347