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Cited by 35Phytochemistry and biological activity of medicinal plantsCancer, Hypoxia, and MetabolismCervical Cancer and HPV Research

Anti-tumor effect of aloe-emodin on cervical cancer cells was associated with human papillomavirus E6/E7 and glucose metabolism

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Gao, Rui, Wu, Xiaowen, Huang, Zhi, Wang, Bi, Li, Fenghu, Xu, Hui, Ran, Li·2019·OncoTargets and Therapy
DOI 10.2147/ott.s182405PMC PMC6526183
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Abstract

Background： Aloe-emodin, an anthraquinone present in aloe latex, has been shown to have anti-proliferative properties in cervical cancer disease, all cases of which are almost caused by human papillomavirus (HPV), with the products of E6/E7. It is suggested that aloe-emodin may play an important role in HPV-induced cervical cancer cells. Methods： Hela and SiHa cells were treated with various concentrations of aloe-emodin. MTT assay and flow cytometry were used to identify the cell growth and apoptosis. The expressions of HPV E6, E7 and GLUT1 (glucose transporter-1) were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot (WB). The glucose uptake, lactate production and ATP production in HeLa and SiHa cells were also investigated. Result： The results indicate that aloe-emodin promoted the apoptosis of HeLa and SiHa cells and decreased the expressions of HPV-related protein E6 and E7. Furthermore, aloe-emodin inhibited glucose metabolism by reducing GLUT1 expression. Overexpression of GLUT1 significantly weakened the apoptosis induced by aloe-emodin in HeLa cells. Conclusion： In this study, we found that aloe-emodin induce apoptosis of cervical cancer cells, which was associated with HPV E6 and E7 and glucose metabolism. Keywords: cervical cancer, aloe-emodin, E6/E7, glucose metabolism

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  • Emodin induces apoptosis in cervical cancer cells through suppression of HPV E6/E7 expression and modulation of glucose metabolism.

    “Moreover, in addition to its lipid metabolism modulatory functions, emodin has also been shown to induce apoptosis in cervical cancer cells through the suppression of HPV E6/E7 expression and modulation of glucose metabolism.277”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [277]

    The Introduction and Discussion report that aloe-emodin (AE) promoted apoptosis in HeLa and SiHa cells, reduced HPV E6/E7 expression, and affected glucose metabolism. The cited study tests aloe-emodin, not emodin as the citing sentence states; it also describes the E6/E7 link as an association rather than establishing that suppression causes apoptosis. (LLM, conf=0.88)

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  1. [1]Lin ML, Lu YC, Chung JG, et al. Down-regulation of MMP-2 through the p38 MAPK-NF-kappaB-dependent pathway by aloe-emodin leads to inhibition of nasopharyngeal carcinoma cell invasion. Mol Carcinog. 2010; 49(9): 783– 797. doi: 10.1002/mc.20652 20607722 · DOI
  2. [2]Xiao BX, Guo J. [The anti-proliferation and anti-migration dual effects of aloe-emodin on KB cells and its mechanism]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2009; 44(1): 50– 52. 19489261
  3. [3]Jeon W, Jeon YK, Nam MJ. Apoptosis by aloe-emodin is mediated through down-regulation of calpain-2 and ubiquitin-protein ligase E3A in human hepatoma Huh-7 cells. Cell Biol Int. 2012; 36(2): 163– 167. doi: 10.1042/CBI20100723 21861846 · DOI
  4. [4]Guo JM, Xiao BX, Liu Q, Zhang S, Liu DH, Gong ZH. Anticancer effect of aloe-emodin on cervical cancer cells involves G2/M arrest and induction of differentiation. Acta Pharmacol Sin. 2007; 28(12): 1991– 1995. doi: 10.1111/j.1745-7254.2007.00707.x 18031614 · DOI
  5. [5]Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2): 74– 108. 15761078
  6. [6]Yoshikawa H. [Progress in the world and challenges in Japan on HPV vaccination for cervical cancer prevention]. Gan To Kagaku Ryoho. 2010; 37(6): 971– 975. 20567096
  7. [7]Ellenson LH, Wu TC. Focus on endometrial and cervical cancer. Cancer Cell. 2004; 5(6): 533– 538. doi: 10.1016/j.ccr.2004.05.029 15193256 · DOI
  8. [8]Zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002; 2(5): 342– 350. doi: 10.1038/nrc798 12044010 · DOI
  9. [9]Ghittoni R, Accardi R, Hasan U, Gheit T, Sylla B, Tommasino M. The biological properties of E6 and E7 oncoproteins from human papillomaviruses. Virus Genes. 2010; 40(1): 1– 13. doi: 10.1007/s11262-009-0412-8 19838783 · DOI
  10. [10]Mesri EA, Feitelson MA, Munger K. Human viral oncogenesis: a cancer hallmarks analysis. Cell Host Microbe. 2014; 15(3): 266– 282. doi: 10.1016/j.chom.2014.02.011 24629334 PMC3992243 · DOI
  11. [11]McLaughlin-Drubin ME, Munger K. Oncogenic activities of human papillomaviruses. Virus Res. 2009; 143(2): 195– 208. doi: 10.1016/j.virusres.2009.06.008 19540281 PMC2730997 · DOI
  12. [12]Brahimi-Horn C, Pouyssegur J. The role of the hypoxia-inducible factor in tumor metabolism growth and invasion. Bull Cancer. 2006; 93(8): E73– E80. 16935775
  13. [13]Macheda ML, Rogers S, Best JD. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol. 2005; 202(3): 654– 662. doi: 10.1002/jcp.20166 15389572 · DOI · Paper page
  14. [14]Birnbaum MJ, Haspel HC, Rosen OM. Cloning and characterization of a cDNA encoding the rat brain glucose-transporter protein. Proc Natl Acad Sci U S A. 1986; 83(16): 5784– 5788. 3016720 PMC386379
  15. [15]Rudlowski C, Becker AJ, Schroder W, Rath W, Buttner R, Moser M. GLUT1 messenger RNA and protein induction relates to the malignant transformation of cervical cancer. Am J Clin Pathol. 2003; 120(5): 691– 698. doi: 10.1309/4KYN-QM58-62JW-2GD7 14608894 · DOI
  16. [16]Cantuaria G, Fagotti A, Ferrandina G, et al. GLUT-1 expression in ovarian carcinoma: association with survival and response to chemotherapy. Cancer. 2001; 92(5): 1144– 1150. 11571727
  17. [18]Haber RS, Rathan A, Weiser KR, et al. GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor prognosis. Cancer. 1998; 83(1): 34– 40. 9655290
  18. [19]Liao H, Wang Z, Deng Z, Ren H, Li X. Curcumin inhibits lung cancer invasion and metastasis by attenuating GLUT1/MT1-MMP/MMP2 pathway. Int J Clin Exp Med. 2015; 8(6): 8948– 8957. 26309547 PMC4538170
  19. [20]Guo JM, Xiao BX, Dai DJ, Liu Q, Ma HH. Effects of daidzein on estrogen-receptor-positive and negative pancreatic cancer cells in vitro. World J Gastroenterol. 2004; 10(6): 860– 863. 15040033 PMC4726994
  20. [21]Pecere T, Gazzola MV, Mucignat C, et al. Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors. Cancer Res. 2000; 60(11): 2800– 2804. 10850417
  21. [22]Mijatovic S, Maksimovic-Ivanic D, Radovic J, et al. Anti-glioma action of aloe emodin: the role of ERK inhibition. Cell Mol Life Sci. 2005; 62(5): 589– 598. doi: 10.1007/s00018-005-4425-8 15747063 PMC11365865 · DOI
  22. [23]Huang SS, Hao DZ, Zhang Y, Liu HM, Shan WS. Progress in studies of the mechanisms and clinical diagnosis of cervical carcinoma associated with genomic integration of high-risk human papillomavirus DNA. Yi Chuan. 2017; 39(9): 775– 783. doi: 10.16288/j.yczz.17-151 28936976 · DOI
  23. [24]Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646– 674. doi: 10.1016/j.cell.2011.02.013 21376230 · DOI · Paper page
  24. [25]Warburg O. On the origin of cancer cells. Science. 1956; 123(3191): 309– 314. 13298683
  25. [26]Shim H, Dolde C, Lewis BC, et al. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci U S A. 1997; 94(13): 6658– 6663. 9192621 PMC21214
  26. [27]Faubert B, Li KY, Cai L, et al. Lactate metabolism in human lung tumors. Cell. 2017; 171(2): 358– 371.e359. doi: 10.1016/j.cell.2017.09.019 28985563 PMC5684706 · DOI · Paper page
  27. [28]Fan R, Hou WJ, Zhao YJ, et al. Overexpression of HPV16 E6/E7 mediated HIF-1α upregulation of GLUT1 expression in lung cancer cells. Tumour Biol. 2016; 37(4): 4655– 4663. doi: 10.1007/s13277-015-4221-5 26508030 · DOI

Cited by

Sorted by citations

Authors
Gao, R., Wu, X., Huang, Z., Wang, B., Li, F., Xu, H., & Ran, L.
Affiliations
Guiyang Medical University (CN)
Corresponding author
Xu, Hui
ORCID
Venue
OncoTargets and Therapy
Publisher
Informa UK Limited
Published
2019-05
Volume
Volume 12
Pages
3713-3721
ISSN
1178-6930 (ISSN-L)
DOI
10.2147/ott.s182405
PMC
PMC6526183
OpenAlex
W2946399080
Cited by
35
References
1
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 4 · 2019: 3
FWCI
3.50
Type
journal article
Language
en
Open access
Licence
Locations
  • OncoTargets and Therapy (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and biological activity of medicinal plants
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
Keywords
aloe-emodin, cervical cancer, human papillomavirus, E6 oncoprotein, E7 oncoprotein, glucose metabolism, GLUT1, apoptosis, anthraquinones, HeLa cells, SiHa cells, glucose uptake, lactic acid production, ATP production

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