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DOI: 10.1055/a-1099-9786
Identification of Flavonoids and Bufadienolides and Cytotoxic Effects of Kalanchoe daigremontiana Extracts on Human Cancer Cell Lines
Publication History
received 22 August 2019
revised 30 December 2019
accepted 10 January 2020
Publication Date:
28 January 2020 (online)
Abstract
Kalanchoe species are well-known medicinal plants used in traditional medicine as anti-inflammatory and analgesic remedies. Recently, it has been reported that Kalanchoe plants have cytotoxic properties; however, data on traditional use of these plants in tumor treatment are extremely limited. Kalanchoe daigremontiana is one of the most popular species cultivated in Europe, and it is used, among other things, as a remedy in treating skin injuries and wounds. Studies on the biological activity of this species are scarce, and there is a lack of data on the cytotoxic activity of K. daigremontiana extracts on epithelial cancer cells in the literature. In our present study, we analyzed the phytochemical composition of K. daigremontiana ethanol extract and fractions–water and dichloromethane–by the HPLC-DAD-ESI-MS method and estimated cytotoxic activity of the extracts on human adenocarcinoma (HeLa), ovarian (SKOV-3), breast (MCF-7), and melanoma (A375) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, real-time cell analyzer (RTCA), and flow cytometry. We identified 6 bufadienolide compounds and 19 flavonoids, mostly kaempferol, quercetin, isorhamnetin, and myricetin glycosides, of which only 3 flavonoids have been identified in K. daigremontiana to date. Other flavonoids that were characterized in our study have not yet been found in this plant. The ethanol extract and water fraction of K. daigremontiana did not show significant cytotoxic activity on the tested cell lines. In contrast, the dichloromethane fraction showed the strongest activity against all cell lines with IC50 values of ≤ 10 µg/mL. The results indicated that this activity is mainly due to the presence of bersaldegenin-1,3,5-orthoacetate.
Supporting Information
- Supporting Information
The dose-response curves leading to the IC50 determinations of the extracts and compound are provided as Supporting Information.
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References
- 1 Milad R, El-Ahmady S, Singab AN. Genus Kalanchoe (Crassulaceae): a review of its ethnomedicinal, botanical, chemical and pharmacological properties. European J Med Plants 2014; 4: 86-104
- 2 Kolodziejczyk-Czepas J, Stochmal A. Bufadienolides of Kalanchoe species: an overview of chemical structure, biological activity and prospects for pharmacological use. Phytochem Rev 2017; 16: 1155-1171
- 3 Quazi Majaz A, Tatiya AU, Khurshid M, Nazim S, Siraj S. The miracle plant (Kalanchoe pinnata): a phytochemical and pharmacological review. Int J Res Ayurveda Pharm 2011; 2: 1478-1482
- 4 Lans CA. Ethanomedicines used in Trinidad and Tobago for urinary problems and diabetes mellitus. J Ethnobiol Ethnomed 2006; 2: 45
- 5 Bussmann RW. Ethnobotany of the Samburu of Mt. Nyiru, South Turkana, Kenya. J Ethnobiol Ethnomed 2006; 2: 35
- 6 Tugume P, Kakudidi EK, Buyinza M, Namaalwa J, Kamaterasi M, Mucunguzi P, Kalema J. Ethnobotanical survey of medicinal plant species used by communities around Mabira Central Forest Reserve, Uganda. J Ethnobiol Ethnomed 2016; 12: 5
- 7 Johnson T. CRC Ethnobotany Desk Reference. Florida: CRC Press LLC; 1999: 448
- 8 Urmenyi FGG, Saraiva GN, Casanova LM, Matos AS, Camargo LMM, Romanos MTV, Costa SS. Anti-HSV-1 and HSV-2 flavonoids and a new kaempferol triglycoside from the medicinal plant Kalanchoe daigremontiana . Chem Biodivers 2016; 13: 1707-1714
- 9 Chanaj-Kaczmarek J, Ulikowska M, Dudek-Makuch M. Investigation on biological activity of the juice from leaves of Kalanchoe daigremontiana . Post Fitoter 2019; 20: 3-9
- 10 Nahar K, Khan MGU, Rahman MS, Begum B, Rashid MA. Antimicrobial and cytotoxic activities of Bryophyllum daigremontianum . J Pharmacol Sci 2008; 7: 99-101
- 11 Bogucka-Kocka A, Zidorn C, Kasprzycka M, Szymczak G, Szewczyk K. Phenolic acid content, antioxidant and cytotoxic activities of four Kalanchoe species. Saudi J Biol Sci 2018; 25: 622-630
- 12 Kolodziejczyk-Czepas J, Nowak P, Wachowicz B, Piechocka J, Głowacki R, Moniuszko-Szajwaj B, Stochmal A. Antioxidant efficacy of Kalanchoe daigremontiana bufadienolide-rich fraction in blood plasma in vitro . Pharm Biol 2016; 54: 3182-3188
- 13 Supratman U, Fujita T, Akiyama K, Hayashi H. Insecticidal compounds from Kalanchoe daigremontiana x tubiflora . Phytochemistry 2001; 58: 311-314
- 14 Moniuszko-Szajwaj B, Pecio Ł, Kowalczyk M, Stochmal A. New bufadienolides isolated from the roots of Kalanchoe daigremontiana (Crassulaceae). Molecules 2016; 21: 243
- 15 Kruk J, Pisarski A, Szymańska R. Novel vitamin E forms in leaves of Kalanchoe daigremontiana and Phaseolus . J Plant Physiol 2011; 168: 2021-2027
- 16 Karsten U, Müller-Stoll WR. Über einige Inhaltsstoffe der bakteriellen Tumoren von Bryophyllum daigremontianum (Hamet et Perr.) Berg. Die Kulturpfanze 1973; 21: 313-329
- 17 Nielsen AH, Olsen CE, Moller BL. Flavonoids in flowers of 16 Kalanchoe blossfeldiana varieties. Phytochemistry 2005; 66: 2829-2835
- 18 Mabry J, Markham KR, Thomas MB. The systematic Identification of Flavonoids. Berlin: Springer; 1970
- 19 Wei LL, Qiu YL, Li QW. Two new prenylated isoflavones from Sedum aizoon L. Fitoterapia 2011; 82: 405-407
- 20 Oufir M, Seiler C, Gerodetti M, Gerber J, Fürer K, Mennet-von Eiff M, Elsas SM, Brenneisen R, von Mandach U, Hamburger M, Potterat O. Quantification of bufadienolides in Bryophyllum pinnatum leaves and manufactured products by UHPLC-ESIMS/MS. Planta Med 2015; 81: 1190-1197
- 21 Zhang L, Yu Z, Wang Y, Wang X, Zhang L, Wang C, Yue Q, Wang X, Deng S, Huo X, Tian X, Huang S, Zhang B, Ma X. Quantitative proteomics reveals molecular mechanism of gamabufotalin and its potential inhibition on Hsp90 in lung cancer. Oncotarget 2016; 7: 76551-76564
- 22 Schoner W, Scheiner-Bobis G. Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth. Am J Physiol Cell Physiol 2007; 293: 509-536
- 23 Tang N, Shi L, Yu Z, Dong P, Wang C, Huo X, Zhang B, Huang S, Deng S, Liu K, Ma T, Wang X, Wu L, Ma XC. Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis by suppressing VEGFR-2 signaling pathway. Oncotarget 2016; 7: 3533-3547
- 24 Huang HC, Lin MK, Yang HL, Hseu YC, Liaw CC, Tseng YH, Tsuzuki M, Kuo YH. Cardenolides and bufadienolide glycosides from Kalanchoe tubiflora and evaluation of cytotoxicity. Planta Med 2013; 79: 1362-1369
- 25 Daniel D, Süsal C, Kopp B, Opelz G, Terness P. Apoptosis-mediated selective killing of malignant cells by cardiac steroids: maintenance of cytotoxicity and loss of cardiac activity of chemically modified derivatives. Int Immunopharmacol 2003; 3: 1791-1801
- 26 Supratman U, Fujita T, Akiyama K, Hayashi H, Murakami A, Sakai H, Koshimizu K, Ohigashi H. Anti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora . Biosci Biotechnol Biochem 2001; 65: 947-949
- 27 Yamagishi T, Haruna M, Yan XZ, Chang JJ, Lee KH. Antitumor agents, 110, bryophyllin B, a novel potent cytotoxic bufadienolide from Bryophyllum pinnatum . J Nat Prod 1989; 52: 1071-1079
- 28 Wu PL, Hsu YL, Wu TS, Bastow KF, Lee KH. Kalanchosides A–C, new cytotoxic bufadienolides from the aerial parts of Kalanchoe gracilis . Org Lett 2006; 8: 5207-5210
- 29 Puschett JB, Agunanne E, Uddin MN. Emerging role of the bufadienolides in cardiovascular and kidney diseases. Am J Kidney Dis 2010; 56: 359-370
- 30 Cheng GH. Advances in quality determination, pharmacological studies and clinical application of toad venom. Zhong Cao Yao 2001; 32: 184-186
- 31 Gao H, Popescu R, Kopp B, Wang Z. Bufadienolides and their antitumor activity. Nat Prod Rep 2011; 28: 953-969
- 32 Hu K, Zhu L, Liang H, Hu F, Feng J. Improved antitumor efficacy and reduced toxicity of liposomes containing bufadienolides. Arch Pharm Res 2011; 34: 1487-1494
- 33 Alvarado-Palacios QG, San Martin-Martinez E, Gomez-Garcia C, Estanislao-Gomez CC, Casañas-Pimentel R. Nanoencapsulation of the Aranto (Kalanchoe daigremontiana) aquoethanolic extract by nanospray dryer and its selective effect on breast cancer cell line. Int J Pharmacogn Phytochem Res 2015; 7: 888-895