CLEISTANTHIN B SHOWS A POTENT CYTOTOXIC ACTIVITY AGAINST COLORECTAL CANCER CELLS
DOI:
https://doi.org/10.22159/ajpcr.2022.v15i3.43953Keywords:
Cleistanthus collinus, Cleistanthin B, In vitro, Cytotoxicity, Apoptosis, Flow cytometry, Anticancer, Colorectal cancerAbstract
Objective: The aim was to find out the cleistanthin B sensitive cancer cell type among a panel of cancer cell lines.
Methods: The 50% inhibitory concentrations (IC50) of cleistanthin B against different cancer cells were determined by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide assay. The cell death caused by cleistanthin B in colorectal cancer (CRC) cells was evaluated by acridine orange and ethidium bromide (AO-EB) dual staining. Using short exposure, we generated the 5-fluorouracil</AQ1> and oxaliplatin (5-FU+Ox) surviving cells from the parental HT-29 CRC cell lines. These surviving CRC cells were further treated with cleistanthin B either alone or combined with 5-FU. Annexin V apoptosis assay was used to determine the combined effect of cleistanthin B with 5-FU against HT-29 cells.
Results: The IC50 values of cleistanthin B were found to be 3.6±0.55, 5.2±0.51, 8.6±1.02, 10.5±1.50, 18.3±3.71, 25.8±5.50, and 26.7±5.90 μg/mL against HT-29, SW-480, HCT-15, HELA, MDA-MB-231, A549, and DU145, respectively. The IC50 value of cleistanthin B against L132 cells was >100 μg/mL. The cleistanthin B treated HT-29, SW-480, and HCT-15 CRC cells showed apoptotic changes such as chromatin condensation, nuclear fragmentation, and formation of apoptotic bodies in the AO-EB dual staining method. Flow cytometry analysis revealed that cleistanthin B enhances the 5-FU induced apoptosis against 5-FU+Ox surviving HT-29 CRC cells.
Conclusion: Cleistanthin B is relatively more potent against CRC cells than other cancer cells, and it induces apoptosis mediated cell death in CRC cells. Cleistanthin B enhances the anticancer activity of 5-FU against HT-29 CRC cells.
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Mathur P, Sathishkumar K, Chaturvedi M, Das P, Sudarshan KL, Santhappan S, et al. Cancer statistics, 2020: Report from national cancer registry programme, India. J Glob Oncol 2020;6:1063-75.
Pucci C, Martinelli C, Ciofani G. Innovative approaches for cancer treatment: Current perspectives and new challenges. Ecancermedicalscience 2019;13:961.
Sen T, Samanta SK. Medicinal plants, human health and biodiversity: A broad review. Adv Biochem Eng Biotechnol 2015;147:59-110.
Chrispal A. Cleistanthus collinus poisoning. J Emerg Trauma Shock 2012;5:160-6.
Mohan A, Naik GS, Harikrishna J, Kumar DP, Rao MH, Sarma K, et al. Cleistanthus collinus poisoning: Experience at a medical intensive care unit in a tertiary care hospital in South India. Indian J Med Res 2016;143:793-7.
Parasuraman S, Raveendran R. Diuretic effects of cleistanthin A and cleistanthin B from the leaves of Cleistanthus collinus in Wistar rats. J Young Pharm 2012;4:73-7.
Govindachari TR, Sathe SS, Viswanathan N, Pai BR, Srinivasan M. Chemical constituents of Cleistanthus collinus (Roxb.). Tetrahedron 1969;25:2815-21.
Woodard JL, Huntsman AC, Patel PA, Chai HB, Kanagasabai R, Karmahapatra S, et al. Synthesis and antiproliferative activity of derivatives of the phyllanthusmin class of arylnaphthalene lignan lactones. Bioorg Med Chem 2018;26:2354-64.
Li S, Liang Z, Li J, Zhang X, Zheng R, Zhao C. Update on naturally occurring novel arylnaphthalenes from plants. Phytochem Rev 2020;19:337-403.
Susplugas S, Hung NV, Bignon J, Thoison O, Kruczynski A, Sévenet T, et al. Cytotoxic Arylnaphthalene lignans from a Vietnamese Acanthaceae, Justicia patentiflora. J Nat Prod 2005;68:734-8.
Lakshmanan M, Bobby Z, Ramasamy R. Action of Cleistanthins A and B on alpha adrenoceptors in rats. J Young Pharm 2016;8:177-85.
Parasuraman S, Raveendran R, Selvaraj RJ. Effects of cleistanthins A and B on blood pressure and electrocardiogram in Wistar rats. Z Naturforsch C J Biosci 2011;66:581-7.
Thummar VR, Parasuraman S, Basu D, Raveendran R. Evaluation of in vivo antitumor activity of cleistanthin B in Swiss albino mice. J Tradit Complement Med 2016;6:383-8.
Kumar CP, Pande G, Shanmugam G. Cleistanthin B causes G1 arrest and induces apoptosis in mammalian cells. Apoptosis 1998;3:413-9.
Parasuraman S, Raveendran R. Effect of cleistanthin A and B on adrenergic and cholinergic receptors. Pharmacogn Mag 2011;7:243-7.
Kumar P, Nagarajan A, Uchil PD. Analysis of cell viability by the MTT assay. Cold Spring Harb Protoc 2018;2018:467-71.
Kasibhatla S, Amarante-Mendes GP, Finucane D, Brunner T, Bossy- Wetzel E, Green DR. Acridine orange/ethidium bromide (AO/EB) staining to detect apoptosis. CSH Protoc 2006;2006:4493.
Yu Y, Kanwar SS, Patel BB, Nautiyal J, Sarkar FH, Majumdar APN. Elimination of colon cancer stem-like cells by the combination of curcumin and FOLFOX. Transl Oncol 2009;2:321-8.
Wlodkowic D, Skommer J, Darzynkiewicz Z. Flow cytometry-based apoptosis detection. Methods Mol Biol 2009;559:19-32.
Chen H, Liu P, Zhang T, Gao Y, Zhang Y, Shen X, et al. Effects of diphyllin as a novel V-ATPase inhibitor on TE-1 and ECA-109 cells. Oncol Rep 2018;39:921-8.
Ren Y, de Blanco EJ, Fuchs JR, Soejarto DD, Burdette JE, Swanson SM, et al. Potential anticancer agents characterized from selected tropical plants. J Nat Prod 2019;82:657-79.
Felth J, Rickardson L, Rosén J, Wickström M, Fryknäs M, Lindskog M, et al. Cytotoxic effects of cardiac glycosides in colon cancer cells, alone and in combination with standard chemotherapeutic drugs. J Nat Prod 2009;72:1969-74.
Anderson SE, Barton CE. The cardiac glycoside convallatoxin inhibits the growth of colorectal cancer cells in a p53-independent manner. Mol Genet Metab Rep 2017;13:42-5.
Calderón-Montaño JM, Burgos-Morón E, Orta ML, Maldonado- Navas D, García-Domínguez I, López-Lázaro M. Evaluating the cancer therapeutic potential of cardiac glycosides. Biomed Res Int 2014;2014:794930.
Reed JC. Apoptosis-targeted therapies for cancer. Cancer Cell 2003;3:17-22.
Sharif S, O’Connell MJ, Yothers G, Lopa S, Wolmark N. FOLFOX and FLOX regimens for the adjuvant treatment of resected stage II and III colon cancer. Cancer Investig 2008;26:956-63.
Hu T, Li Z, Gao CY, Cho CH. Mechanisms of drug resistance in colon cancer and its therapeutic strategies. World J Gastroenterol 2016;22:6876-89.
Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: Mechanisms of action and clinical strategies. Nat Rev Cancer 2003;3:330-8.
Wang P, Yang HL, Yang YJ, Wang L, Lee SC. Overcome cancer cell drug resistance using natural products. Evid Based Complement Alternat Med 2015;2015:767136.
Swift LH, Golsteyn RM. Genotoxic anticancer agents and their relationship to DNA damage, mitosis, and checkpoint adaptation in proliferating cancer cells. Int J Mol Sci 2014;15:3403-31.
Prabhakaran C, Kumar P, Panneerselvam N, Rajesh S, Shanmugam G. Cytotoxic and genotoxic effects of cleistanthin B in normal and tumour cells. Mutagenesis 1996;11:553-7.
El Khoury F, Corcos L, Durand S, Simon B, Le Jossic-Corcos C. Acquisition of anticancer drug resistance is partially associated with cancer stemness in human colon cancer cells. Int J Oncol 2016;49:2558-68.
Carey PJ. Drug-induced myelosuppression: Diagnosis and management. Drug Saf 2003;26:691-706.
Schurig JE, Florczyk AP, Bradner WT. The mouse as a model for predicting the myelosuppressive effects of anticancer drugs. Cancer Chemother Pharmacol 1986;16:243-6.
Lozupone F, Borghi M, Marzoli F, Azzarito T, Matarrese P, Iessi E, et al. TM9SF4 is a novel V-ATPase-interacting protein that modulates tumor pH alterations associated with drug resistance and invasiveness of colon cancer cells. Oncogene 2015;34:5163-74.
Kettimuthu KP, Lourthuraj AA, Manickam AS, Subramani S, Ramachandran A. Mechanisms of toxicity of Cleistanthus collinus: Vacuolar ATPases are a putative target. Clin Toxicol (Phila) 2011;49:457-63.
Nampoothiri K, Chrispal A, Begum A, Jasmine S, Gopinath KG, Zachariah A. A clinical study of renal tubular dysfunction in Cleistanthus collinus (Oduvanthalai) poisoning. Clin Toxicol (Phila) 2010;48:193-7
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