You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic. For video creation, please contact our Academic Video Service.
Version Summary Created by Modification Content Size Created at Operation
1 Alan Prem Kumar -- 1444 2023-01-17 08:21:30 |
2 format correct Conner Chen + 2 word(s) 1446 2023-01-18 04:05:32 |

Video Upload Options

We provide professional Academic Video Service to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Tuli, H.S.;  Rath, P.;  Chauhan, A.;  Ranjan, A.;  Ramniwas, S.;  Sak, K.;  Aggarwal, D.;  Kumar, M.;  Dhama, K.;  Lee, E.H.C.; et al. Anti-Cancer Mechanisms of Cucurbitacins. Encyclopedia. Available online: https://encyclopedia.pub/entry/40265 (accessed on 13 December 2025).
Tuli HS,  Rath P,  Chauhan A,  Ranjan A,  Ramniwas S,  Sak K, et al. Anti-Cancer Mechanisms of Cucurbitacins. Encyclopedia. Available at: https://encyclopedia.pub/entry/40265. Accessed December 13, 2025.
Tuli, Hardeep Singh, Prangya Rath, Abhishek Chauhan, Anuj Ranjan, Seema Ramniwas, Katrin Sak, Diwakar Aggarwal, Manoj Kumar, Kuldeep Dhama, E Hui Clarissa Lee, et al. "Anti-Cancer Mechanisms of Cucurbitacins" Encyclopedia, https://encyclopedia.pub/entry/40265 (accessed December 13, 2025).
Tuli, H.S.,  Rath, P.,  Chauhan, A.,  Ranjan, A.,  Ramniwas, S.,  Sak, K.,  Aggarwal, D.,  Kumar, M.,  Dhama, K.,  Lee, E.H.C.,  Yap, K.C.,  Capinpin, S.M., & Kumar, A.P. (2023, January 17). Anti-Cancer Mechanisms of Cucurbitacins. In Encyclopedia. https://encyclopedia.pub/entry/40265
Tuli, Hardeep Singh, et al. "Anti-Cancer Mechanisms of Cucurbitacins." Encyclopedia. Web. 17 January, 2023.
Anti-Cancer Mechanisms of Cucurbitacins
Edit
This entry is adapted from the peer-reviewed paper 10.3390/biom13010057

Cucurbitacins constitute a group of cucumber-derived dietary lipids, highly oxidized tetracyclic triterpenoids, with potential medical uses. These compounds are known to interact with a variety of recognized cellular targets to impede the growth of cancer cells.

cucurbitacins anti-proliferation apoptotic

1. Apoptotic and Cell-Cycle Arrest

Apoptotic cell death can be triggered in cancer through internal and extrinsic processes, which converge on the control of caspase-dependent proteolysis of cellular proteins and DNA fragmentation [1][2][3]. Similarly, all tumor types have abnormal cell-cycle progression activity, which acts as a catalyst for carcinogenesis [4]. Recent research has shown that a variety of biological processes are regulated by cell-cycle proteins [5][6][7]. Therefore, numerous chemo-preventive FDA-drugs have been shown to mediate antitumor effects either via activation of apoptotic or cell-cycle arrest (Figure 1) signaling pathways [8][9][10]. For instance, results from Li et al. (2018) revealed that cucurbitacin I caused lung cancer (A549) cells to undergo excessive ERS, CHOP-Bax and caspase-12-dependent ERS-associated apoptosis [11]. In colorectal cancer (SW480 and Caco-2) cells, treatment with cucurbitacin B resulted in cell-cycle arrest at the G1 phase as well as decreased Cyclin D1 and Cyclin E1 levels. Both CRC cell lines underwent in vitro cell death when exposed to cucurbitacin B (CuB), which was accompanied by caspase-3 and cleaved PARP [12]. Using triple negative breast cancer (TNBC), cucurbitacin E strongly boosted JNK activation while considerably decreasing AKT and ERK activation in MDA-MB-468 cells. It also significantly decreased expression of Cyclin D1, Survivin, XIAP, Bcl2 and Mcl-1 [13]. In the pancreatic cancer cell line Capan-1, CuD induced cell-cycle arrest and death via the ROS/p38 pathway [14]. Cucurbitacin I-induced cell death in ovarian cancer (SKOV3) included apoptosis, as evidenced by upregulated caspase 3 and BAX and a decrease in Bcl2 [15]. Flow cytometric measurement of DNA content and RT-PCR analyses suggested that cucurbitacin B caused G2/M arrest in human breast cancer cell lines (MDA-MB-231 and MCF-7) through elevated p21 expression [16]. Huang et al. showed that in human bladder cancer (T24) cells, cucurbitacin E-induced G2/M arrest was accompanied by a significant rise in p53 and p21 levels and a fall in the levels of STAT3, cyclin-dependent kinase 1 (CDK1) and cyclin B [17]. In addition, cucurbitacin E-induced G2/M phase arrest and death of T24 cells also depended on Fas/CD95 and mitochondria-dependent apoptotic pathways. Similarly, using other cancerous cell lines, cucurbitacins target the cell-cycle actions that involves growth inhibition, cell-cycle arrest at G2/M phase and induction of apoptosis [18]. Cucurbitacin I has been observed to suppress phosphotyrosine STAT3 in human cancerous lung cells [19]. Recently, it was observed to promote gastric cancer cell apoptosis by inducing the production of cellular ROS, as well as the endoplasmic reticulum stress pathway [11][20]. While cucurbitacin B, E and I have been observed to inhibit both JAK2 and STAT3 activation, cucurbitacin A and I have been reported to inhibit JAK2 and STAT3, respectively [19]. Treating Hep-2 cells with different concentrations of cucurbitacin B for various time intervals showed reduction in cell proliferation, cell-cycle distribution, and increased cell apoptosis in cancerous cell lines [18]. This study also stated that cucurbitacin B exhibited significant efficacy in inhibiting cell growth, arresting cell cycle at the G2/M phase, and inducing apoptosis in a dose- and time-dependent manner [18]. Similarly, cucurbitacins B, D, E were observed to inhibit proteins such as JAK-STAT3. They also inhibited mitogen-activated protein kinases (MAPK)- signaling pathways and tumor angiogenesis [20]. A study conducted on human umbilical vascular endothelial cell lines revealed cucurbitacin to significantly inhibit the proliferation, migration, and angiogenesis. It also blocked essential proteins such as Jak2-signal transducer, vascular endothelial growth factor receptor (VEGFR) and STAT3 signaling pathways [21]. Such studies have highlighted that the main mechanism involved in imparting the anti-tumorigenic potentials of cucurbitacins involves inhibition of the JAK/STAT3 signaling pathway, which plays an essential role in activation, proliferation, and maintenance of cancerous cells [22]. Another recent study has shown that treatment with 8 µM cucurbitacin IIb for 24 h remarkably inhibited the proliferation of HeLa and A549 tumor cells, with IC50 values of 7.3 and 7.8 µM, respectively, while increasing total apoptosis by 56.9 and 52.3%, respectively [23]. Another pathway by which cucurbitacin IIb induces apoptosis and cell-cycle arrest is by the regulating EGFR/MAPK pathway [24]. Similarly, cucurbitacin D was observed to regulate the levels of oncogenic signaling cascades, JAK/STAT, Wnt/β-catenin and associated non-coding RNAs in many cancer cell lines [25]. Recent studies have shown that CuIIb and cucurbitacin B induced apoptosis in cervical cancer cell lines by Nrf2 inhibition, whereas in lung cancer cell lines cucurbitacin B was responsible for suppressing growth and inducing apoptotic death by impeding IL-6/STAT3 signaling [15][26].
Biomolecules 13 00057 g002 550
Figure 1. Molecular targets of cucurbitacins in modulating cell-cycle progression and inducing apoptotic cell death.

2. Antiangiogenic and Antimetastatic Mechanisms

The physiological process by which new blood vessels develop from pre-existing vessels is known as angiogenesis. Anti-angiogenesis causes suppression of tumor growth because of hunger and toxic waste buildup in its microenvironment [27][28]. The development and metastasis of the tumor have a major impact on the cancer vasculature (Figure 2). Vascular endothelial growth factors (VEGFs) are crucial protein regulators of angiogenesis and metastasis. Studies have shown that inhibiting the VEGFR2-mediated JAK/STAT3 pathway is considered as an effective approach to suppress angiogenesis [21]. Though many studies about the mechanism of cucurbitacins and angiogenesis are not well known, few studies have still shown that cucurbitacins such as cucurbitacin B, cucurbitacin D, cucurbitacin E and cucurbitacin I possess anti-angiogenesis properties [29][30]. CuB significantly inhibited angiogenesis, metastasis, and vascular development in dose-dependent manner in in vivo models and chick embryos [29]. CuE significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation and angiogenesis by targeting the VEGFR2-mediated Jak2/STAT3 signaling pathway [21]. CuB has been observed to inhibit ERK1/2, prevent Raf-MEK-ERK from activating STAT3, which ultimately plays a key role in angiogenesis [31]. A similar effect of CuB was seen also in human breast cancer cell lines. It successfully inhibited angiogenesis by targeting the FAK/MMP-9 signaling axis [32]. CuB showed antimetastatic activity and targeted angiogenesis also in paclitaxel resistant A2780/Taxol ovarian cancer cells. It also suppressed angiogenesis by downregulating the expression of HIF-1 targets, VEGF, VEGFR2 phosphorylation and erythropoietin [29][33]. Another study revealed the effective use of CuE for anti-angiogenesis in Huh7 cells. It decreased the tube formation in HUVECs and was also responsible for inhibiting the process of neo-vascularization in CAM assays [34]. A recent study showed that CuE modulated the JAK/STAT3 pathways, which regulated the angiogenesis [35]. CuE has been also involved in inhibiting the KDR/VEGFR2-mediated pathway of angiogenesis [36]. Treating A549 cells with cucurbitacins for ~21 days showed positive results for inhibiting metastasis by regulating the levels of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D11 [37]. Similarly, other cucurbitacins were observed to inhibit angiogenesis in MDA-MB-231 and MCF-7 cancer cells by inhibiting the JAK/STAT pathways [38].
Biomolecules 13 00057 g003 550
Figure 2. Molecular targets of cucurbitacins in suppressing angiogenesis and impeding cancer cell metastasis.

3. Anti-Inflammatory Mechanisms

Most malignancies’ growth and malignant progression are correlated with inflammation [39][40][41]. Both intrinsic and extrinsic inflammations have the potential to inhibit the immune system, which creates an ideal environment for the growth of tumors [42][43][44]. As a result, focusing on inflammation is a tempting strategy for both cancer therapy and cancer prevention [42][45]. Cucurbitacins have been observed to interact with proteins associated with inflammatory (Figure 3) pathways such as interleukins (IL)-6, IL-5, IL-1β, IL-12, IL-13 in a dose-dependent manner [46]. Dietary cucurbitacin E has been shown to reduce inflammation and immunosuppression by downregulating the NF-κB signaling pathway [47]. CuB has been studied to possess protective effects by reducing inflammatory responses on sepsis-induced acute lung injury in in vivo rat models. It significantly reduced the levels of TNF-α, IL-6, cytokine secretion and accumulation of inflammatory cells. It also regulated the levels of Ca2+, which play an essential role in inflammatory responses [48]. CuB inhibited inflammatory responses through targeting the SIRT1/IGFBPrP1/TGF β1 axis. It downregulated the expression levels of TGF β1, IGFBPrP1, and upregulated the expression of SIRT 1 [49]. Similarly, CuE decreased the levels of pro-inflammatory cytokines, such as IL-17 and IFN-γ, as well as the activities of the STAT3 and IL-17A-promoter in allo-reactive T cells [50]. CuE has been shown to inhibit skin inflammation and fibrosis by regulating the expression of α-Sma and Col-I in mice models [49]. Recently, it has also been demonstrated that CuE ameliorated lipopolysaccharide-evoked injuries and inflammation in bronchial epithelial cells by regulating the TLR4-NF-κB signaling. It was responsible for suppressing levels of inflammatory cytokine production, TNF-α, IL-6 and IL-8 [51]. Cucurbitacin B was observed to directly bind to toll-like receptor 4 (TLR4) and activate NLRP3 inflammasome, which further ultimately executed pyroptosis in A549 cells. CuB treatment has been observed to upregulate the protein expressions of IL-1β, GSDMD, HMGB1 and led to inhibition of generation of mitochondrial ROS and pyroptosis [52]. CuB was reported to sensitize CD133+ HepG2 cells in in vitro and in vivo models [53].
Biomolecules 13 00057 g004 550
Figure 3. Anti-inflammatory targets of cucurbitacins in malignant cells.

References

  1. Manu, K.A.; Shanmugam, M.K.; Li, F.; Chen, L.; Siveen, K.S.; Ahn, K.S.; Kumar, A.P.; Sethi, G. Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products. J. Mol. Med. 2014, 92, 267–276.
  2. Sethi, G.; Kwang, S.A.; Sandur, S.K.; Lin, X.; Chaturvedi, M.M.; Aggarwal, B.B. Indirubin enhances tumor necrosis factor-induced apoptosis through modulation of nuclear factor-kappa B signaling pathway. J. Biol. Chem. 2006, 281, 23425–23435.
  3. Jung, Y.Y.; Um, J.Y.; Chinnathambi, A.; Govindasamy, C.; Sethi, G.; Ahn, K.S. Leelamine Modulates STAT5 Pathway Causing Both Autophagy and Apoptosis in Chronic Myelogenous Leukemia Cells. Biology 2022, 11, 366.
  4. Chopra, P.; Sethi, G.; Dastidar, S.G.; Ray, A. Polo-like kinase inhibitors: An emerging opportunity for cancer therapeutics. Expert Opin. Investig. Drugs 2010, 19, 27–43.
  5. Xiao, W.; Li, J.; Hu, J.; Wang, L.; Huang, J.R.; Sethi, G.; Ma, Z. Circular RNAs in cell cycle regulation: Mechanisms to clinical significance. Cell Prolif. 2021, 54, 13143.
  6. Raghunath, A.; Sundarraj, K.; Arfuso, F.; Sethi, G.; Perumal, E. Dysregulation of Nrf2 in Hepatocellular Carcinoma: Role in Cancer Progression and Chemoresistance. Cancers 2018, 10, 481.
  7. Ma, Z.; Xiang, X.; Li, S.; Xie, P.; Gong, Q.; Goh, B.C.; Wang, L. Targeting hypoxia-inducible factor-1, for cancer treatment: Recent advances in developing small-molecule inhibitors from natural compounds. Semin. Cancer Biol. 2022, 80, 379–390.
  8. Rajendran, P.; Ong, T.H.; Chen, L.; Li, F.; Shanmugam, M.K.; Vali, S.; Abbasi, T.; Kapoor, S.; Sharma, A.; Kumar, A.P.; et al. Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo. Clin. Cancer Res. 2011, 17, 1425–1439.
  9. Ahn, K.S.; Sethi, G.; Aggarwal, B.B. Simvastatin potentiates TNF-alpha-induced apoptosis through the down-regulation of NF-kappaB-dependent antiapoptotic gene products: Role of IkappaBalpha kinase and TGF-beta-activated kinase-1. J. Immunol. 2007, 178, 2507–2516.
  10. Mohan, C.D.; Rangappa, S.; Nayak, S.C.; Jadimurthy, R.; Wang, L.; Sethi, G.; Garg, M.; Rangappa, K.S. Bacteria as a treasure house of secondary metabolites with anticancer potential. Semin. Cancer Biol. 2021, 86, 998–1013.
  11. Li, H.; Chen, H.; Li, R.; Xin, J.; Wu, S.; Lan, J.; Xue, K.; Li, X.; Zuo, C.; Jiang, W.; et al. Cucurbitacin I induces cancer cell death through the endoplasmic reticulum stress pathway. J. Cell. Biochem. 2018, 120, 2391–2403.
  12. Mao, D.; Liu, A.H.; Wang, Z.P.; Zhang, X.W.; Lu, H. Cucurbitacin B inhibits cell proliferation and induces cell apoptosis in colorectal cancer by modulating methylation status of BTG3. Neoplasma 2019, 66, 593–602.
  13. Kong, Y.; Chen, J.; Zhou, Z.; Xia, H.; Qiu, M.H.; Chen, C. Cucurbitacin E induces cell cycle G2/M phase arrest and apoptosis in triple negative breast cancer. PLoS ONE 2014, 9, e103760.
  14. Kim, M.S.; Lee, K.; Ku, J.M.; Choi, Y.J.; Mok, K.; Kim, D.; Cheon, C.; Ko, S.G. Cucurbitacin D Induces G2/M Phase Arrest and Apoptosis via the ROS/p38 Pathway in Capan-1 Pancreatic Cancer Cell Line. Evid. Based. Complement. Alternat. Med. 2020, 2020, 6571674.
  15. Vidal-Gutiérrez, M.; Torres-Moreno, H.; Arenas-Luna, V.; Loredo-Mendoza, M.L.; Tejeda-Dominguez, F.; Velazquez, C.; Vilegas, W.; Hernández-Gutiérrez, S.; Robles-Zepeda, R.E. Standardized phytopreparations and cucurbitacin IIb from Ibervillea sonorae (S. Watson) greene induce apoptosis in cervical cancer cells by Nrf2 inhibition. J. Ethnopharmacol. 2022, 298, 115606.
  16. Duangmano, S.; Sae-Lim, P.; Suksamrarn, A.; Patmasiriwat, P.; Domann, F.E. Cucurbitacin B Causes Increased Radiation Sensitivity of Human Breast Cancer Cells via G2/M Cell Cycle Arrest. J. Oncol. 2012, 2012, 601682.
  17. Huang, W.W.; Yang, J.S.; Lin, M.W.; Chen, P.Y.; Chiou, S.M.; Chueh, F.S.; Lan, Y.H.; Pai, S.J.; Tsuzuki, M.; Ho, W.J.; et al. Cucurbitacin E Induces G(2)/M Phase Arrest through STAT3/p53/p21 Signaling and Provokes Apoptosis via Fas/CD95 and Mitochondria-Dependent Pathways in Human Bladder Cancer T24 Cells. Evid. Based. Complement. Alternat. Med. 2012, 2012, 952762.
  18. Liu, T.; Zhang, M.; Zhang, H.; Sun, C.; Deng, Y. Inhibitory effects of cucurbitacin B on laryngeal squamous cell carcinoma. Eur. Arch. Otorhinolaryngol. 2008, 265, 1225–1232.
  19. Blaskovich, M.A.; Sun, J.; Cantor, A.; Turkson, J.; Jove, R.; Sebti, S.M. 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-PubMed. Cancer Res. 2003, 63, 1270–1279.
  20. Liang, J.; Chen, D. Advances in research on the anticancer mechanism of the natural compound cucurbitacin from Cucurbitaceae plants: A review. Tradit. Chin. Med. 2019, 4, 68.
  21. Dong, Y.; Lu, B.; Zhang, X.; Zhang, J.; Lai, L.; Li, D.; Wu, Y.; Song, Y.; Luo, J.; Pang, X.; et al. Cucurbitacin E, a tetracyclic triterpenes compound from Chinese medicine, inhibits tumor angiogenesis through VEGFR2-mediated Jak2-STAT3 signaling pathway. Carcinogenesis 2010, 31, 2097–2104.
  22. Wu, D.; Wang, Z.; Lin, M.; Shang, Y.; Wang, F.; Zhou, J.Y.; Wang, F.; Zhang, X.; Luo, X.; Huang, W. In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product from Cucumber. Front. Pharmacol. 2019, 10, 1287.
  23. Torres-Moreno, H.; Marcotullio, M.C.; Velázquez, C.; Ianni, F.; Garibay-Escobar, A.; Robles-Zepeda, R.E. Cucurbitacin IIb, a steroidal triterpene from Ibervillea sonorae induces antiproliferative and apoptotic effects on cervical and lung cancer cells. Steroids 2020, 157, 108597.
  24. Liang, Y.; Zhang, T.; Ren, L.; Jing, S.; Li, Z.; Zuo, P.; Li, T.; Wang, Y.; Zhang, J.; Wei, Z. Cucurbitacin IIb induces apoptosis and cell cycle arrest through regulating EGFR/MAPK pathway. Environ. Toxicol. Pharmacol. 2021, 81, 103542.
  25. Lin, X.; Farooqi, A.A. Cucurbitacin mediated regulation of deregulated oncogenic signaling cascades and non-coding RNAs in different cancers: Spotlight on JAK/STAT, Wnt/β-catenin, mTOR, TRAIL-mediated pathways. Semin. Cancer Biol. 2021, 73, 302–309.
  26. Liu, J.H.; Li, C.; Cao, L.; Zhang, C.H.; Zhang, Z.H. Cucurbitacin B regulates lung cancer cell proliferation and apoptosis via inhibiting the IL-6/STAT3 pathway through the lncRNA XIST/miR-let-7c axis. Pharm. Biol. 2022, 60, 154–162.
  27. Siveen, K.S.; Ahn, K.S.; Ong, T.H.; Shanmugam, M.K.; Li, F.; Yap, W.N.; Kumar, A.P.; Fong, C.W.; Tergaonkar, V.; Hui, K.M.; et al. Y-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model. Oncotarget 2014, 5, 1897–1911.
  28. Wu, Q.; You, L.; Nepovimova, E.; Heger, Z.; Wu, W.; Kuca, K.; Adam, V. Hypoxia-inducible factors: Master regulators of hypoxic tumor immune escape. J. Hematol. Oncol. 2022, 15, 77.
  29. Piao, X.M.; Gao, F.; Zhu, J.X.; Wang, L.J.; Zhao, X.; Li, X.; Sheng, M.M.; Zhang, Y. Cucurbitacin B inhibits tumor angiogenesis by triggering the mitochondrial signaling pathway in endothelial cells. Int. J. Mol. Med. 2018, 42, 1018–1025.
  30. Sheikh, I.; Sharma, V.; Tuli, H.S.; Aggarwal, D.; Sankhyan, A.; Vyas, P.; Sharma, A.K.; Bishayee, A. Cancer Chemoprevention by Flavonoids, Dietary Polyphenols and Terpenoids. Biointerface Res. Appl. Chem. 2021, 11, 8502–8537.
  31. Yin, B.; Fang, D.M.; Zhou, X.L.; Gao, F. Natural products as important tyrosine kinase inhibitors. Eur. J. Med. Chem. 2019, 182, 111664.
  32. Sinha, S.; Khan, S.; Shukla, S.; Lakra, A.D.; Kumar, S.; Das, G.; Maurya, R.; Meeran, S.M. Cucurbitacin B inhibits breast cancer metastasis and angiogenesis through VEGF-mediated suppression of FAK/MMP-9 signaling axis. Int. J. Biochem. Cell Biol. 2016, 77, 41–56.
  33. Garg, S.; Kaul, S.C.; Wadhwa, R. Cucurbitacin B and cancer intervention: Chemistry, biology and mechanisms (review). Int. J. Oncol. 2018, 52, 19–37.
  34. Liu, Y.; Yang, H.; Guo, Q.; Liu, T.; Jiang, Y.; Zhao, M.; Zeng, K.; Tu, P. Cucurbitacin E Inhibits Huh7 Hepatoma Carcinoma Cell Proliferation and Metastasis via Suppressing MAPKs and JAK/STAT3 Pathways. Molecules 2020, 25, 560.
  35. Ramezani, M.; Hasani, M.; Ramezani, F.; Abdolmaleki, M.K. Cucurbitacins: A focus on Cucurbitacin E as a natural product and their biological activities. Pharm. Sci. 2020, 27, 1–13.
  36. Yun, W.; Dan, W.; Liu, J.; Guo, X.; Li, M.; He, Q. Investigation of the Mechanism of Traditional Chinese Medicines in Angiogenesis through Network Pharmacology and Data Mining. Evid.-Based Complement. Altern. Med. 2021, 2021, 5539970.
  37. Ren, Y.; Kinghorn, A.D. Natural Product Triterpenoids and Their Semi-Synthetic Derivatives with Potential Anticancer Activity. Planta Med. 2019, 85, 802–814.
  38. Sathya, T.N.; Mehta, V.A.; Senthil, D.; Navaneethakrishnan, K.; Murugan, S.; Kumaravel, T. Cytotoxicity evaluation of CELNORM, a nutritional health supplement, on MCF7 breast cancer cells. Indian J. Sci. Technol. 2020, 13, 3070–3075.
  39. Ong, P.S.; Wang, L.Z.; Dai, X.; Tseng, S.H.; Loo, S.J.; Sethi, G. Judicious Toggling of mTOR Activity to Combat Insulin Resistance and Cancer: Current Evidence and Perspectives. Front. Pharmacol. 2016, 7, 395.
  40. Ma, Z.; Wang, Y.Y.; Xin, H.W.; Wang, L.; Arfuso, F.; Dharmarajan, A.; Kumar, A.P.; Wang, H.; Tang, F.R.; Warrier, S.; et al. The expanding roles of long non-coding RNAs in the regulation of cancer stem cells. Int. J. Biochem. Cell Biol. 2019, 108, 17–20.
  41. Ashrafizadeh, M.; Zarrabi, A.; Mostafavi, E.; Aref, A.R.; Sethi, G.; Wang, L.; Tergaonkar, V. Non-coding RNA-based regulation of inflammation. Semin. Immunol. 2022, 59, 101606.
  42. Morgan, D.; Garg, M.; Tergaonkar, V.; Tan, S.Y.; Sethi, G. Pharmacological significance of the non-canonical NF-κB pathway in tumorigenesis. Biochim. Biophys. Acta Rev. Cancer 2020, 1874, 188449.
  43. Cheng, J.T.; Wang, L.; Wang, H.; Tang, F.R.; Cai, W.Q.; Sethi, G.; Xin, H.W.; Ma, Z. Insights into Biological Role of LncRNAs in Epithelial-Mesenchymal Transition. Cells 2019, 8, 1178.
  44. Cai, W.; Chen, Z.X.; Rane, G.; Singh, S.S.; Choo, Z.; Wang, C.; Yuan, Y.; Tan, T.Z.; Arfuso, F.; Yap, C.T.; et al. Wanted DEAD/H or Alive: Helicases Winding Up in Cancers. J. Natl. Cancer Inst. 2017, 109, djw278.
  45. Ong, S.K.L.; Shanmugam, M.K.; Fan, L.; Fraser, S.E.; Arfuso, F.; Ahn, K.S.; Sethi, G.; Bishayee, A. Focus on Formononetin: Anticancer Potential and Molecular Targets. Cancers 2019, 11, 611.
  46. Kapoor, N.; Ghorai, S.M.; Kushwaha, P.K.; Shukla, R.; Aggarwal, C.; Bandichhor, R. Plausible mechanisms explaining the role of cucurbitacins as potential therapeutic drugs against coronavirus 2019. Inform. Med. Unlocked 2020, 21, 100484.
  47. Xie, H.; Tuo, X.; Zhang, F.; Bowen, L.; Zhao, W.; Xu, Y. Dietary cucurbitacin E reduces high-strength altitude training induced oxidative stress, inflammation and immunosuppression. An. Acad. Bras. Cienc. 2020, 92, 1–14.
  48. Hua, S.; Liu, X.; Lv, S.; Wang, Z. Protective Effects of Cucurbitacin B on Acute Lung Injury Induced by Sepsis in Rats. Med. Sci. Monit. 2017, 23, 1355.
  49. Yang, L.; Ao, Q.; Zhong, Q.; Li, W.; Li, W. SIRT1/IGFBPrP1/TGF β1 axis involved in cucurbitacin B ameliorating concanavalin A-induced mice liver fibrosis. Basic Clin. Pharmacol. Toxicol. 2020, 127, 371–379.
  50. Kim, S.Y.; Park, M.J.; Kwon, J.E.; Jung, K.A.; Jhun, J.Y.; Lee, S.Y.; Seo, H.B.; Ryu, J.Y.; Beak, J.A.; Choi, J.Y.; et al. Cucurbitacin E ameliorates acute graft-versus-host disease by modulating Th17 cell subsets and inhibiting STAT3 activation. Immunol. Lett. 2018, 203, 62–69.
  51. Shang, J.; Liu, W.; Yin, C.; Chu, H.; Zhang, M. Cucurbitacin E ameliorates lipopolysaccharide-evoked injury, inflammation and MUC5AC expression in bronchial epithelial cells by restraining the HMGB1-TLR4-NF-κB signaling. Mol. Immunol. 2019, 114, 571–577.
  52. Yuan, R.; Zhao, W.; Wang, Q.Q.; He, J.; Han, S.; Gao, H.; Feng, Y.; Yang, S. Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. Pharmacol. Res. 2021, 170, 105748.
  53. Wang, X.; Bai, Y.; Yan, X.; Li, J.; Lin, B.; Dai, L.; Xu, C.; Li, H.; Li, D.; Yang, T.; et al. Cucurbitacin B exhibits antitumor effects on CD133+ HepG2 liver cancer stem cells by inhibiting JAK2/STAT3 signaling pathway. Anticancer. Drugs 2021, 32, 548–557.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Oncology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Hardeep Singh Tuli , Prangya Rath , Abhishek Chauhan , Anuj Ranjan , Seema Ramniwas , Katrin Sak , Diwakar Aggarwal , Manoj Kumar , Kuldeep Dhama ,
E Hui Clarissa Lee
, Kenneth Chun-Yong Yap , Sharah Mae Capinpin , Alan Prem Kumar
View Times: 1.1K
Revisions: 2 times (View History)
Update Date: 18 Jan 2023
Table of Contents
    Notice
    You are not a member of the advisory board for this topic. If you want to update advisory board member profile, please contact office@encyclopedia.pub.
    OK
    Confirm
    Only members of the Encyclopedia advisory board for this topic are allowed to note entries. Would you like to become an advisory board member of the Encyclopedia?
    Yes
    No
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    There is no comment~
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    ${ selectedItem.replyTextCharacter }/${ selectedItem.replyMaxCharacter }
    Submit
    Cancel
    Confirm
    Are you sure to Delete?
    Yes No
    Academic Video Service
    Feedback