The phytochemicals are categorised as micronutrients, macronutrients, and secondary metabolites. Cucurbitacins are mainly found in the Cucurbitaceae family, which consists of 965 plant species in 120 genera. Aribi A, Gery S, Lee DH, Thoennissen NH, Thoennissen GB, Alvarez R, Ho Q, Lee K, Doan NB, Chan KT. Before 2004;52:345–9. The value of bioactive compounds of cruciferous vegetables (Brassica) as antimicrobials and antioxidants: a review. Cell Death Dis. Cucurbitacin D exhibits its anti-cancer effect in human breast cancer ... Cucurbits have been also to stimulate the central nervous system and to treat dizziness. Journal of Translational Medicine Papers with duplicate titles, abstracts and pharmacological experiments that included homoeopathic preparations associated with cucurbitacins were excluded. Novel Triterpenoid Alkaloids With Their Potential Cytotoxic Activity From the Roots of. Pediatric Ophthalmology and Adult Strabismus Clinic at the Kellogg Eye Center in Ann Arbor. Targeting Akt, NF-κB, and Stat3 may also be useful for treating breast cancer. Furthermore, cucurbitacin B acts as a mediator in the distribution and reorganization of cytoskeletal proteins via RAC1/CDC42/RhoA signaling, altering the mechanical properties of MDA‐MB‐231 and SKBR‐3 breast cancer cells. Our study clearly demonstrates that cucurbitacin D inhibited Akt, NF-κB, and Stat3 . 2022;22:354. colocynthis has the highest amount of cucurbitacin E and cucurbitacins E-Glu in the leaves and fruit (Davidovich-Rikanati et al., 2015; Kim et al., 2018).In C. melo, the concentration of cucurbitacin B is highest in the leaves, fruit and roots, in that order (Luo et al., 2020). Martinez et al. One of the most extensive plant families distributed worldwide is Brassicaceae, which comprises almost 400 genera and 4000 species. Graziani EI, Allen TM, Andersen RJ. The excessive ERS levels additionally prompted autophagic cell death [76]. This high mortality rate is primarily due to the insensitivity of pancreatic cancer to most chemotherapy and radiotherapy treatments. The therapeutic anticancer potential of cucurbitacins depends on the quality and quantity of the bioactive compounds contained, the soil in which the plants are grown and the geographical location of these species. 2020;44:e13414. Yar Saglam A, Alp E, Elmazoglu Z, Menevse S. Treatment with cucurbitacin B alone and in combination with gefitinib induces cell cycle inhibition and apoptosis via EGFR and JAK/STAT pathway in human colorectal cancer cell lines. All authors listed have made a substantial, direct, and intellectual contribution to the review. Hum Exp Toxicol. Olmedo D, Rodríguez N, Vásquez Y, Solis P, Lopez-Perez J, Feliciano AS, Gupta M. A new coumarin from the fruits of Coutarea hexandra. This particular integrin plays a role in tumour formation and angiogenesis, and cucurbitacin B was able to inhibit angiogenesis in human microvascular endothelial cells, dose-dependently, in concentrations as low as 100 nM [69]. evaluated the anticancer potential of Cucurbita moschata in an in vitro model, using K562 human leukaemia cells, B16 murine melanoma cells, and A549 lung adenocarcinoma cells. [14, 41, 42]. Planta Med. Afr J Tradit Complement Altern Med. There are currently some reports linking a wide spectrum of bioactivity of these secondary metabolites to the prevention and treatment of several chronic diseases, such as obesity, type 2 diabetes, cardiovascular diseases, cancer, and osteoporosis. Zhang et al. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. BMC Complement Altern Med. J Adv Res. Furthermore, a special kind of cucurbitacins from the Cucurbitaceae family called momordicosides can be found in the Momordica charantia (bitter melon or African cucumber). 2021;2021:6349041. 2016 Apr;34(2):139-48. doi: 10.1007/s10637-015-0317-4. From the chemical point of view, cucurbitacins are cucurbitane-type tetracyclic triterpenoid saponins with 30 carbons atoms on their basic skeleton (the detailed chemical data can be found in Figures S1, S2 and S3 and Table 1, and the synthesis of cucurbitacins in Figures S4 to S12, in the Additional file 1). These alterations lead to apoptosis increase and cause arrest at the G2/M cell cycle phase. Ul Haq F, Ali A, Khan MN, Shah SMZ, Kandel RC, Aziz N, Adhikari A, Choudhary MI, El-Seedi HR, Musharraf SG. Nonetheless, some studies have also reported the presence of cucurbitacins in both the fungi and the animal kingdom. Aiswarya SUD, Vikas G, Haritha NH, Liju VB, Shabna A, Swetha M, Rayginia TP, Keerthana CK, Nath LR, Reshma MV, et al. FOIA Am J Chin Med. 2022;22:239. However, since most of the reported studies were performed in vitro, further in vivo work either on model animals or human clinical trials needs to be executed. Furthermore, antioxidant activity, as well as antimicrobial capacity have also been detailed. 2021;38:4659–73. J Transl Med. This is evidenced by a substantial increase in the activity of Caspase 3/7 in the human prostate cancer cell lines LNCaP and PC-3, as opposed to normal prostate epithelial cells (PrEC), an increase in the Sub-G0/G1 phase, but also cleavage of Poly (ADP-ribose) polymerase, involved in DNA repair. Cucumis melo is well known for its beneficial pharmacological assets, such as analgesic, anti-inflammatory, antioxidant, antiulcer, anticancer, antimicrobial, diuretic, antidiabetic, hepatoprotective, and immunomodulator [31]. Kellogg Eye Center - Ann Arbor | Michigan Medicine A . Cole S, Gianferante DM, Zhu B, Mirabello L. Osteosarcoma: a surveillance, epidemiology, and end results program-based analysis from 1975 to 2017. Therefore, cucurbitacins are a class of promising anticancer drugs to be used alone or be intergraded in current chemotherapies and radiotherapies to treat many types of cancers. Using de novo assembled transcriptomics from I. amara, gene co-expression analysis and comparative genomics, we unraveled the evolutionary origin of the insect deterrent cucurbitacins in I. amara. The synergistic effect of Cucurbitacin B and radiation treatment. Kirdeeva Y, Fedorova O, Daks A, Barlev N, Shuvalov O. It also interfered with the activity of the GTPases RAC1 and CDC42, which are important regulators of cell tension, thereby impacting cell migration in vitro and in vivo breast cancer models. 1 Altmetric Metrics Abstract As the main substance in some traditional Chinese medicines, cucurbitacins have been used to treat hepatitis for decades in China. Pharmacogn Rev. This inhibition is dependent on PP2A activity, and this study showed that the triterpenoid may target CIP2A to reactivate PP2A [60]. Cancer Cell Int. Cucumber bitterness explained | OSU Extension Service Cucurbitacin Q was found to be the most abundant in C. pareira, while Citrullus colocynthis contained all four cucurbitacins in abundant quantities. Human papilloma virus: apprehending the link with carcinogenesis and unveiling new research avenues (Review). The same authors also found that cucurbitacin B can inhibit the expression and nuclear translocation of β-catenin, a key participator in cancer development and metastasis, by suppressing the expression of Wnt3 and Wnt3a ligands, commonly overexpressed in NSCLC [63]. Fruit bitterness requires both Bi and the dominant Bt (Bitter fruit) gene. Federal government websites often end in .gov or .mil. 2022;11:1885. Aquilaria agallocha (Thymelaeaceae family) is one of the largest producers of agarwood used throughout history in religious ceremonies, herbal medicines and perfumes, and whose composition is rich in cucurbitacins particularly E and I) [47]. Data on cucurbitacins and their anticancer activities were collected from databases such as PubMed/MedLine, TRIP database, Web of Science, Google Scholar, and ScienceDirect and the information was arranged sequentially for a better understanding of the antitumor potential. Notably, the expressions of ERK1 and MEK1 were significantly downregulated when compared with non-treated cells [78]. Ungureanu A, Zlatian O, Mitroi G, Drocas A, Tirca T, Calina D, Dehelean C, Docea AO, Izotov BN, Rakitskii VN, et al. Thus, co-administering chemotherapeutic agents with natural products may offer a synergistic effect [85]. J Asian Nat Prod Res. Wu et al. 2015;56:175–81. Hou X, Meehan EJ, Xie J, Huang M, Chen M, Chen L. Atomic resolution structure of cucurmosin, a novel type 1 ribosome-inactivating protein from the sarcocarp of Cucurbita moschata. Jing SY, Wu ZD, Zhang TH, Zhang J, Wei ZY. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Disclaimer. 2017 Jan 13;14(2):75-82. doi: 10.21010/ajtcam.v14i2.9. volume 20, Article number: 630 (2022) Therefore, establishing the distributions of secondary metabolites in this family is of utmost importance. Treatment with the molecule led to an overexpression of CDK1 mRNA, which accumulates during the G1 phase, increasing the activity of CDK1 over the intermediate level necessary for the G1/S transition. 2014;349:15–25. Klungsaeng S, Kukongviriyapan V, Prawan A, Kongpetch S, Senggunprai L. Targeted modulation of FAK/PI3K/PDK1/AKT and FAK/p53 pathways by cucurbitacin B for the antiproliferation effect against human cholangiocarcinoma cells. Would you like email updates of new search results? Cucurbitacin B induces autophagy and apoptosis by suppressing CIP2A/PP2A/mTORC1 signaling axis in human cisplatin resistant gastric cancer cells. Chem Pharm Bull. Domino's Farms Petting Farm. 2012;12:185. SCH772984 increased significantly cucurbitacin B sensitivity in pancreatic cancer cells but not in normal pancreatic ductal epithelial cells (used as a control) [89]. Furthermore, the generation of ROS was linked to phosphorylation of p38 and c-Jun. Cancers (Basel). They confirmed that isolated compounds from this vegetable inhibit cell tumour growth by working like ribosome-inactivating proteins [17, 29, 30]. Zhang J, Song Y, Liang Y, Zou H, Zuo P, Yan M, Jing S, Li T, Wang Y, Li D, et al. Cogn. Similarly, cucurbitacin IIb isolated from Ibervillea sonorae was tested as an antitumoural treatment option for NSCLC in the A549 cell line, reducing cell growth and inducing apoptosis at low concentrations and in a dose-dependent manner, while also inhibiting STAT3 expression and suppressing the activity of EGFR and/or of its downstream proteins [80]. 2016;64:946–52. Javed Z, Khan K, Herrera-Bravo J, Naeem S, Iqbal MJ, Raza Q, Sadia H, Raza S, Bhinder M, Calina D, et al. 2007;9:525–9. These compounds presented strong cytotoxic effects against the following cancer cell lines: gastric (NUGC-3), nasopharyngeal (HONE-1), breast (MCF-7) and lung (A549) [43]. Most of them are consumed in vegetables or in fruits, but they also show medicinal value, the reason why they have been used for traditional medicine in China [24]. Nevertheless, detailed information about those functional ingredients in cucumber is scarce. Rom J Morphol Embryol. Lee J-S, Maarisit W, Abdjul DB, Yamazaki H, Takahashi O, Kirikoshi R, Kanno S-I, Namikoshi M. Structures and biological activities of triterpenes and sesquiterpenes obtained from Russula lepida. Melim C, Lauro MR, Pires IM, Oliveira PJ, Cabral C. The role of glucosinolates from cruciferous vegetables (Brassicaceae) in gastrointestinal cancers: from prevention to therapeutics. Biomed Res Int. Despite recent advances in cancer therapies, breast cancer remains the second leading cause of death among women [94,95,96,97]. Int J Pharm Clin Res. Specifically, the triterpenoid induced gene expression of CDKN1A and CDKN2A and downregulated the tumour promoter gene, hindering cellular growth and promoting apoptosis. 2004;67:1823–8. Chen X, Bao J, Guo J, Ding Q, Lu J, Huang M, Wang Y. Anticancer Drugs. Cucurbitacin - Wikipedia 2021;21:318–318. Ali ES, Mitra K, Akter S, Ramproshad S, Mondal B, Khan IN, Islam MT, Sharifi-Rad J, Calina D, Cho WC. 1 Cucurbitacin is a diverse family of organic compounds, all of which are highly oxygenated tetracyclic triterpenes. Cucurbitacin D combined with doxorubicin significantly increased p-p53 levels and suppressed p-Akt, p-NF-κB, p-Stat3, and Bcl-2 levels more than doxorubicin or cucurbitacin D alone. Nutrients. Phytochemistry. Die Pharmazie-Int J Pharm Sci. 2021;12:1886. [13][14][15] The 2-O-β-D-glucopyranosides of cucurbitacins K and L can be extracted with ethanol from fruits of Cucurbita pepo cv dayangua. detected a dose- and time-dependent cytotoxicity. Previous studies on the anti-tumour mechanism of CuB have mostly focused on cell apoptosis, and research on the ferroptosis-inducing effect has rarely been reported. Accessibility In vivo testing using MDA-MB-231 injected orthotopically in female athymic nude mice showed up to 50% tumour volume reduction following cucurbitacin B treatment when compared with untreated mice. 2013;132:2730–7. Varela, C., Melim, C., Neves, B.G. Human osteosarcoma is the most common malignant bone tumour occurring in children and teenagers [8]. Zhou J, Zhao T, Ma L, Liang M, Guo Y-J, Zhao L-M. Cucurbitacin B and SCH772984 exhibit synergistic anti-pancreatic cancer activities by suppressing EGFR, PI3K/Akt/mTOR, STAT3 and ERK signaling. 2022;27:3440. Bitter bottle gourd (Lagenaria siceraria) toxicity - PubMed Cancer cells have a low dependence on external proliferative stimuli and often do not need stimulation to multiply; through the mutations of some oncogenes, these cells acquire a proliferative autonomy, producing their mitogenic signals [2, 8, 56]. Bitterness seems to vary with the type of cucumber grown. Cucurbitacins as potential anticancer agents: new insights on molecular mechanisms, https://doi.org/10.1186/s12967-022-03828-3, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/. Interestingly, these cucurbitacins showed modest in vitro cytotoxicity against human ovarian carcinoma (HEY) and human glioblastoma/astrocytoma (U373) cell lines [54]. Bioactive compounds as potential agents for sexually transmitted diseases management: a review to explore molecular mechanisms of action. 2014;5:1812–28. Mol Med Rep. 2017;16:8771–80. 2006;67:2691–6. Rare case of disseminated fusariosis in a young patient with graft vs host disease following an allogeneic transplant. Recent advances and limitations of mTOR inhibitors in the treatment of cancer. Zou J-M, Wang L-S, Ma X-M, Guo Y-J, Shi R-B. HHS Vulnerability Disclosure, Help Cucurbitacins A, B, C, E, I, J, and K and their glycosides are abundant in Cucurbitaceae family members; they induce a cytotoxic activity that inhibits cancer cell proliferation, actin. Sci Rep. 2016;6:36594. Most patients, however, experience tumour recurrences that are resistant to cisplatin. Cucurbitacin B was also found to suppress cell invasion and migration induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) of the hepatoma human cell lines HepG2 and BEL-7402. J Adv Res. How should the worldwide knowledge of traditional cancer healing be integrated with herbs and mushrooms into modern molecular pharmacology? Cancer Res. Induction of ferroptosis in human nasopharyngeal cancer cells by ... Data on the anticancer effects of cucurbitacins, necessary to carry out the current review were obtained by analyzing the following specialized databases PubMed/MedLine, TRIP database, Web of Science, Google Scholar, and ScienceDirect using the following MesH terms: “Antineoplastic Agents, Phytogenic/pharmacology”, “Animals”, “Apoptosis/drug effects”, “Cell Line, Tumor”, “Cell Transformation, Neoplastic/drug effects”, “Cucurbitacins/chemistry”, “Cucurbitacins/pharmacology”, “Cucurbitacins/therapeutic use”, “Drug Design”, “Drug Therapy/Combination” “Humans”, “Molecular Targeted Therapy”, “Neoplasms/drug therapy”, “Neoplasm Invasiveness”, “Neoplasms/pathology”, “Phytotherapy”, “Signal Transduction/drug effects”. Regarding NSCLC, cucurbitacin D proved to be cytostatic on NSCLC-N6 cells, an action associated with cell cycle arrest at the G1 phase. Oncol Lett. [16][7], Cucurbitacins are under basic research for their biological properties, including toxicity and potential pharmacological uses in development of drugs for inflammation, cancer, cardiovascular diseases, and diabetes, among others. The anticancer activity of cucurbitacin B, obtained from the dried rhizome powder of Corallocarpus epigaeus, was determined to induce the apoptotic machinery in the A375 melanoma cell line, by targeting the MAPK pathway and suppressing proliferation. Metabolite profiling and quantitation of cucurbitacins in Cucurbitaceae plants by liquid chromatography coupled to tandem mass spectrometry. The researchers found that cucurbitacin IIa acts as a tyrosine kinase inhibitor of the EGFR, and treatment with the molecule altered the expression of genes in the EGFR/MAPK pathway, namely downregulating the expression of cyclinB1, ERK1, MEK1, and MEK2, and upregulating the survivin, BRAF, Raf1, ERK2, and STAT3 genes. The most common symptoms include diarrhea and hematemesis. Identification of cucurbitacins and assembly of a draft genome for Aquilaria agallocha. Chainitikun S, Saleem S, Lim B, Valero V, Ueno NT. Your privacy choices/Manage cookies we use in the preference centre. 2020;12:258–62. 2021;18:1464. 2016;8:113–23. Wang D-C, Pan H-Y, Deng X-M, Xiang H, Gao H-Y, Cai H, Wu L-J. Tobacco smoking and liver cancer risk: potential avenues for carcinogenesis. Iqbal MJ, Javed Z, Herrera-Bravo J, Sadia H, Anum F, Raza S, Tahir A, Shahwani MN, Sharifi-Rad J, Calina D, Cho WC. Evid Based Complement Alternat Med. Bajalia EM, Azzouz FB, Chism DA, Giansiracusa DM, Wong CG, Plaskett KN, Bishayee A. Lovenone, a cytotoxic degraded triterpenoid isolated from skin extracts of the North Sea dorid nudibranch Adalaria loveni. I.: Structures of hebevinosides I, II, III, IV, and V. Chem Pharm Bull. These stimuli can be authenticated with an analogous ecological role—their intensive bitterness is toxic to a wide range of herbivores, microorganisms, insects, and parasites, thus protecting their hosts from predators [23]. 1911;2021:26. Cucurbitacins belong to the latter classification, representing an intriguing convergence between plants, fungi and even some animals.
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