Activity of Kalanchoe pinnata in Cancer: Comparison
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Kalanchoe pinnata (Lam) Pers. (syn. Bryophyllum pinnatum Lam.), belonging to the genus Kalanchoe, is a succulent plant cultivated in gardens, which can be found as a herb or shrub. The bioactive ingredients in Kalanchoe pinnata, a succulent herb with ethnomedical applications for several diseases, including cancer, and reveal its anticancer mechanisms through a molecular approach.

  • Kalanchoe pinnata
  • phytochemicals
  • antitumor activity

1. Introduction

Cancer is a genetic disease that displays a variety of molecular alterations in the genome of somatic cells [1]. Cancer cells’ traits, such as sustained proliferation, resistance to cell death, angiogenesis capacity, invasion, evasion of immune surveillance, and metastasis, could be the targets of bioactive compounds of medicinal plants. These alterations include small or large structural variations due to epigenetic changes characterized by the addition or removal of chemical groups from/to DNA, histones [2], or RNA [3]. As such, inherited or sporadic mutations cannot only activate oncogenes or deactivate tumor suppressor genes, but may even lead to reversible chemical modifications such as the methylation of DNA, histones, or RNA, which can affect gene expression without changing DNA sequences. Plants from the genus Kalanchoe (Fam: Crassulaceae) have a global distribution in warm climates, where they are used as ornamental plants. Some of the 200 Kalanchoe species are known for their curative uses in different diseases, including cancer. Natural remedies are used on a large scale worldwide, and herbal extracts are obtained from a great variety of plants. At the level of chemical composition, Kalanchoe species include flavonoids, bufadienolides, fatty acids, triterpenoids, alkaloids, phenolic acids, saponins, tannins, glycosides, and kalanchosides [4,5,6][4][5][6]; many of these constituents have remarkable anticancer potential. Numerous studies have evaluated the anticarcinogenic efficacy of these natural bioactive molecules. For example, quercetin has been reported to inhibit the proliferation of human breast cancer cells [7]. Bufadienolides have been shown to have antiangiogenic activity, cause inhibition of cell growth and proliferation, and induce cell death [8]. Antiproliferative activity has also been reported for triterpenes [9] and kalanchosides [5]. Important issues in cancer treatment are drug-related cumulative toxicity and chemoresistance. Hence, combination therapy offers good results due to the use of different targets and reduced adverse effects. Alternative therapy options may include the use of phytochemicals. 
The features of Kalanchoe pinnata (Figure 1) and its phytochemicals, with a focus on the mechanisms underlying its chemopreventive and therapeutic properties.
Figure 1. Taxonomic classification of K. pinnata. Source: Photos by authors, image created with BioRender.com.
Taxonomic classification of K. pinnata. Source: Photos by researchers, image created with BioRender.com.

2. Phytochemical Constituents of Kalanchoe pinnata

Kalanchoe pinnata (Lam) Pers. (syn. Bryophyllum pinnatum Lam.), belonging to the genus Kalanchoe, is a succulent plant cultivated in gardens [11][10], which can be found as a herb or shrub. The plant has opposite, simple, and compound leaves, with a red to dark purple crenate margin. It reproduces from seeds and vegetatively through leaves [12][11], presenting clusters of reddish-purple pendulous flowers [13][12]. K. pinnata is used in traditional medicine to treat different diseases including cancer [6]. Mora-Pérez and Hernández-Medel [14][13] analyzed the ingredients of K. pinnata and found alkaloids and sterols in methanolic root extract, and terpenes, sterols, flavonoids, chlorides, nitrates, and potassium in methanolic stem extract. The leaves of this plant contain phenols (gallic acid), flavonoids (quercetin) (in methanol extract), lycopenes, and β-carotenes (in petroleum ether) [15][14], as well as tannins and alkaloids [16][15]. Jaiswal et al. [17][16] found that the phenolic content of leaves was 28.4 ± 2 µg mg−1 and suggested that this was responsible for their antioxidant capacity. El Abdellaoui et al. [18][17] detected three phenolic acids (gallic, caffeic, and coumaric acids), three flavanol glycosides (quercetin, isorhamnetin, and kaempferol), 4′,5-dihydroxy-3′,8-dimethoxyflavone 7-O-β-D-glucopyranoside, and quercitrin [19][18]. Bufadienolides such as bersaldegenin acetate-2, -3, -4, -5, bryophyllin a, bryophyllin c, and bersaldegenin-1,3,5-orthoacetate [20][19] have also been found. Reported phenanthrene derivatives include Ψ-taraxasterol and 18-α-oleanane, and other ingredients include sterols; bryophynol, bryophyllol, and bryophollone [21][20]; stigmasterol [22][21]; campesterol, 24-epiclerosterol, (24R)-5α-stigmasta-7,25-dien-3β-ol, 5 α-stigmast-24-en-3β-ol, and 25-methyl-5α-ergost-24(28)-en-3β-ol [23][22] (Figure 2). The leaves of K. pinnata are rich in ascorbic acid (vitamin C) and contain riboflavin, thiamine, niacin, magnesium, calcium, potassium, phosphorus, sodium, and microelements such as iron and zinc [16][15]. K. pinnata flowers contain a higher concentration of glycosides [24][23], similar to other Kalanchoe species.
Figure 2.
 Structures of major phytochemicals reported in 
K. pinnata
. Source: Image created with BioRender.com.

3. Activity of Kalanchoe pinnata in Cancer

Several plant components have been identified as sources of anticancer therapeutics. However, those components should be investigated in clinical trials to confirm their pharmacokinetic effects. Members of the Kalanchoe genus (Crassulaceae) have remedial properties for a wide range of diseases such as gastric ulcers, urolithiasis, bacterial, viral, and parasitic infections, skin diseases, cold, memory improvement, or even improvement in sleep quality when undergoing cancer treatment. Based on ethnobotanical evidence, the Kalanchoe genus has been evaluated on various cancer cell lines (Table 1). The phytochemicals present in K. pinnata have been analyzed in a variety of studies on cancer.
Table 1.
 Anticancer properties found in the Kalanchoe genus.
Kalanchoe Subject Effect Study Type Cell Line Reference
K. daigremontiana Raym.-Hamet and H. Perrier Ovarian, cervical, breast cancer, and melanoma Antiproliferative, cytotoxic, and antioxidant activity.

Cell cycle arrest and caspase-independent cell death		 In vitro SCOV-3, HaCaT, HeLa, MCF-7, A375 [8,20,26,27,28][8][19][24][25][26]
K. integra var. crenata (Andr.) Cardiotoxicity by doxorubicin

Colorectal adenocarcinoma, lung cancer, mesothelioma, hepatocarcinoma, breast cancer		 Cardio-protection against cardiotoxicity by cancer therapy

Apoptosis		 In vivo (rats)

In vitro

DLD-1, A549, SPC212, HepG2, MCF-7		 [9,29][9][27]
K. tubiflora (Harvey) Lung cancer

Lung adenocarcinoma, oral adenosquamous carcinoma, melanoma, and leukemia cell lines		 Induction of autophagy

Cell cycle arrest and senescence

Cell cycle arrest and apoptosis

Cytoprotective autophagy		 In vitro

In vitro, in vivo (mice)		 CL1-5

A549, Cal-27, A2058, HL-60		 [30,31,32][28][29][30]
K. gastonis-bonnieri Raym.-Hamet Benign prostatic hyperplasia

Prostate cancer		 Antiproliferative activity and apoptosis induction

Antiproliferative activity, apoptosis induction, and androgen receptor degradation		 In vitro Stromal cells

LAPC-4, LNCaP,

PC-3, DU145		 [33,[3134]][32]
K. flammea Prostate cancer Apoptosis induction and cell cycle arrest In vitro PC-3, LNCaP, PrEC [35][33]
K. laetivirens Lung cancer Reversion of etoposide resistance In vitro A549, A549RT-eto [36][34]
K. gracilis (L.) DC Murine macrophage and human hepatocarcinoma Antiproliferative, antioxidant, and anti-inflammatory activity In vitro RAW264.7, HepG2 [37][35]
K. beharensis Acute myeloid leukemia Apoptosis induction, inhibition of NF-κB In vitro HL-60, HL60R [38][36]
K. brasiliensis Kidney carcinoma Cytotoxic activity In vitro 3T3, 786-0 [39][37]
K. laciniata Baby hamster kidney cell line Cytotoxic activity In vitro in vivo (mice) BHK-21 [40][38]
Plant extracts by themselves do not produce a significant effect against cancer, but they may enhance therapeutic efficacy when combined with chemotherapeutic drugs. The most studied natural compounds are polyphenols, which are widely distributed in plant tissues. These compounds are secondary metabolites produced for protection against bacteria, fungi, and insects. Natural phenols more studied for their properties are curcumin, epigallocatechin-3-gallate, resveratrol, quercetin, and myricetin [25][39], of these compounds, quercetin is found in K. pinnata.

References

  1. Vogelstein, B.; Kinzler, K.W. Cancer genes and the pathways they control. Nat. Med. 2004, 10, 789–799.
  2. Kouzarides, T. Chromatin modifications and their function. Cell 2007, 128, 693–705.
  3. Desrosiers, R.; Friderici, K.; Rottman, F. Identification of Methylated Nucleosides in Messenger RNA from Novikoff Hepatoma Cells. Proc. Natl. Acad. Sci. USA 1974, 71, 3971–3975.
  4. Nielsen, A.H.; Olsen, C.E.; Møller, B.L. Flavonoids in flowers of 16 Kalanchoë blossfeldiana varieties. Phytochemistry 2005, 66, 2829–2835.
  5. Wu, P.-L.; Hsu, Y.-L.; Wu, T.-S.; Bastow, K.F.; Lee, K.-H. Kalanchosides A−C, New Cytotoxic Bufadienolides from the Aerial Parts of Kalanchoe gracilis. Org. Lett. 2006, 8, 5207–5210.
  6. Kamboj, A.; Saluja, A. Bryophyllum pinnatum (Lam.) Kurz.: Phytochemical and Pharmacological Profile: A Review. Phcog. Rev. 2009, 3, 364–374.
  7. Tao, S.-F.; He, H.-F.; Chen, Q. Quercetin inhibits proliferation and invasion acts by up-regulating miR-146a in human breast cancer cells. Mol. Cell. Biochem. 2015, 402, 93–100.
  8. Stefanowicz-Hajduk, J.; Gucwa, M.; Moniuszko-Szajwaj, B.; Stochmal, A.; Kawiak, A.; Ochocka, J.R. Bersaldegenin-1,3,5-orthoacetate induces caspase-independent cell death, DNA damage and cell cycle arrest in human cervical cancer HeLa cells. Pharm. Biol. 2021, 59, 54–65.
  9. Kuete, V.; Fokou, F.W.; Karaosmanoğlu, O.; Beng, V.P.; Sivas, H. Cytotoxicity of the methanol extracts of Elephantopus mollis, Kalanchoe crenata and 4 other Cameroonian medicinal plants towards human carcinoma cells. BMC Complement. Altern. Med. 2017, 17, 280.
  10. Oliver-Bever, B. Medicinal plants in tropical west africa III. Anti-infection therapy with higher plants. J. Ethnopharmacol. 1983, 9, 1–83.
  11. Sandoval, M.C.; Martínez, J.L. El uso de Kalanchoe pinnata (Lam.) Pers. en el estado de Veracruz. Cienc. Hombre 1994, 16, 49–56.
  12. Majaz, Q.; Tatiya, A.U.; 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.
  13. Mora-Pérez, A.; Hernández-Medel, M. Actividad anticonvulsivante del extracto metanólico de tallo y raíz de Kalanchoe pinnata Lam. en ratones: Comparación con diazepam|Elsevier Enhanced Reader. Neurología 2016, 31, 161–168.
  14. Mohan, S.C.; Balamurugan, V.; Salini, S.T.; Rekha, R. Metal ion chelating activity and hydrogen peroxide scavenging activity of medicinal plant Kalanchoe pinnata. J. Chem. Pharm. Res. 2012, 4, 197–202.
  15. Okwu, D.E.; Josiah, C. Evaluation of the chemical composition of two Nigerian medicinal plants. Afr. J. Biotechnol. 2006, 5, 357–361.
  16. Jaiswal, S.; Chawla, R.; Sawhney, S. Kalanchoe pinnata—A Promising Source of Natural Antioxidants. Eur. J. Med. Plants 2014, 4, 1210–1222.
  17. El Abdellaoui, S.; Destandau, E.; Toribio, A.; Elfakir, C.; Lafosse, M.; Renimel, I.; André, P.; Cancellieri, P.; Landemarre, L. Bioactive molecules in Kalanchoe pinnata leaves: Extraction, purification, and identification. Anal. Bioanal. Chem. 2010, 398, 1329–1338.
  18. Muzitano, M.F.; Tinoco, L.W.; Guette, C.; Kaiser, C.R.; Rossi-Bergmann, B.; Costa, S.S. The antileishmanial activity assessment of unusual flavonoids from Kalanchoe pinnata. Phytochemistry 2006, 67, 2071–2077.
  19. Stefanowicz-Hajduk, J.; Hering, A.; Gucwa, M.; Hałasa, R.; Soluch, A.; Kowalczyk, M.; Stochmal, A.; Ochocka, R. Biological activities of leaf extracts from selected Kalanchoe species and their relationship with bufadienolides content. Pharm. Biol. 2020, 58, 732–740.
  20. Siddiqui, S.; Faizi, S.; Siddiqui, B.S.; Sultana, N. Triterpenoids and phenanthrenes from leaves of Bryophyllum pinnatum. Phytochemistry 1989, 28, 2433–2438.
  21. Anjoo, K.; Saluja, A.K. Isolation of stigmasterol from petroleum ether extract of aerial parts of Bryophyllum pinnatum (Crassulaceae). J. Pharm. Res. 2010, 3, 2802–2803.
  22. Akihisa, T.; Kokke, W.C.M.C.; Tamura, T.; Matsumoto, T. Sterols ofKalanchoe pinnata: First report of the isolation of both C-24 epimers of 24-alkyl-Δ25-sterols from a higher plant. Lipids 1991, 26, 660–665.
  23. McKENZIE, R.A.; Dunster, P.J. Hearts and flowers: Bryophyllum poisoning of cattle. Aust. Vet. J. 1986, 63, 222–227.
  24. Stefanowicz-Hajduk, J.; Hering, A.; Gucwa, M.; Sztormowska-Achranowicz, K.; Kowalczyk, M.; Soluch, A.; Ochocka, J.R. An In Vitro Anticancer, Antioxidant, and Phytochemical Study on Water Extract of Kalanchoe daigremontiana Raym.-Hamet and H. Perrier. Molecules 2022, 27, 2280.
  25. Stefanowicz-Hajduk, J.; Asztemborska, M.; Krauze-Baranowska, M.; Godlewska, S.; Gucwa, M.; Moniuszko-Szajwaj, B.; Stochmal, A.; Ochocka, J.R. Identification of Flavonoids and Bufadienolides and Cytotoxic Effects of Kalanchoe daigremontiana Extracts on Human Cancer Cell Lines. Planta Med. 2020, 86, 239–246.
  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 × butiflora. Biosci. Biotechnol. Biochem. 2001, 65, 947–949.
  27. Asiedu-Gyekye, I.J.; Arhin, E.; Arthur, S.A.; N’Guessan, B.B.; Amponsah, S.K. Genotoxicity, nitric oxide level modulation and cardio-protective potential of Kalanchoe Integra Var. Crenata (Andr.) Cuf Leaves in murine models. J. Ethnopharmacol. 2022, 283, 114640.
  28. Huang, H.-C.; Chang, W.-T.; Lee, M.-S.; Chen, H.-Y.; Chen, Y.-H.; Lin, C.-C.; Lin, M.-K. Three bufadienolides induce cell death in the human lung cancer cell line CL1-5 mainly through autophagy. Bioorganic Med. Chem. Lett. 2021, 31, 127715.
  29. Hsieh, Y.-J.; Huang, H.-S.; Leu, Y.-L.; Peng, K.-C.; Chang, C.-J.; Chang, M.-Y. Anticancer activity of Kalanchoe tubiflora extract against human lung cancer cells in vitro and in vivo. Environ. Toxicol. 2016, 31, 1663–1673.
  30. Huang, H.-C.; Lin, M.-K.; Yang, H.-L.; Hseu, Y.-C.; Liaw, C.-C.; Tseng, Y.-H.; Tsuzuki, M.; Kuo, Y.-H. Cardenolides and Bufadienolide Glycosides from Kalanchoe tubiflora and Evaluation of Cytotoxicity. Planta Med. 2013, 79, 1362–1369.
  31. Palumbo, A.; Casanova, L.; Corrêa, M.F.P.; Da Costa, N.M.; Nasciutti, L.E.; Costa, S.S. Potential Therapeutic Effects of Underground Parts of Kalanchoe gastonis-bonnieri on Benign Prostatic Hyperplasia. Evid.-Based Complement. Altern. Med. 2019, 2019, 6340757.
  32. Shamaladevi, N.; Araki, S.; Lyn, D.A.; Ayyathurai, R.; Gao, J.; Lokeshwar, V.B.; Navarrete, H.; Lokeshwar, B.L. The andean anticancer herbal product BIRM causes destabilization of androgen receptor and induces caspase-8 mediated-apoptosis in prostate cancer. Oncotarget 2016, 7, 84201–84213.
  33. Arias-González, I.; García-Carrancá, A.M.; Cornejo-Garrido, J.; Ordaz-Pichardo, C. Cytotoxic effect of Kalanchoe flammea and induction of intrinsic mitochondrial apoptotic signaling in prostate cancer cells. J. Ethnopharmacol. 2018, 222, 133–147.
  34. Kaewpiboon, C.; Srisuttee, R.; Malilas, W.; Moon, J.; Kaowinn, S.; Cho, I.-R.; Johnston, R.N.; Assavalapsakul, W.; Chung, Y.-H. Extract of Bryophyllum laetivirens reverses etoposide resistance in human lung A549 cancer cells by downregulation of NF-κB. Oncol. Rep. 2014, 31, 161–168.
  35. Lai, Z.-R.; Ho, Y.-L.; Huang, S.-C.; Huang, T.-H.; Lai, S.-C.; Tsai, J.-C.; Wang, C.-Y.; Huang, G.-J.; Chang, Y.-S. Antioxidant, Anti-inflammatory and Antiproliferative Activities of Kalanchoe gracilis (L.) DC Stem. Am. J. Chin. Med. 2011, 39, 1275–1290.
  36. Poma, P.; Labbozzetta, M.; McCubrey, J.A.; Ramarosandratana, A.V.; Sajeva, M.; Zito, P.; Notarbartolo, M. Antitumor Mechanism of the Essential Oils from Two Succulent Plants in Multidrug Resistance Leukemia Cell. Pharmaceuticals 2019, 12, 124.
  37. Fonseca, A.G.; Dantas, L.L.S.F.R.; Fernandes, J.M.; Zucolotto, S.M.; Lima, A.A.N.; Soares, L.A.L.; Rocha, H.A.O.; Lemos, T.M.A.M. In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe brasiliensis (Crassulaceae) Leaves. J. Toxicol. 2018, 2018, 6849765.
  38. Sharif, A.; Akhtar, M.F.; Akhtar, B.; Saleem, A.; Manan, M.; Shabbir, M.; Ashraf, M.; Peerzada, S.; Ahmed, S.; Raza, M. Genotoxic and cytotoxic potential of whole plant extracts of Kalanchoe laciniata by Ames and MTT assay. EXCLI J. 2017, 16, 593–601.
  39. Leri, M.; Scuto, M.; Ontario, M.L.; Calabrese, V.; Calabrese, E.J.; Bucciantini, M.; Stefani, M. Healthy Effects of Plant Polyphenols: Molecular Mechanisms. Int. J. Mol. Sci. 2020, 21, 1250.
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