Aloe-Emodin and Emodin

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Emodin and aloe-emodin are aglycone derivatives found in cascara, as well as other plants, which have been shown to have anticancer properties in numerous in vitro and animal studies.7

Aloe-Emodin

A systematic review identified 38 in vitro studies, which demonstrated that aloe-emodin inhibits cancer cell proliferation, migration, and invasion and induces cell cycle arrest and apoptosis.8 Mechanisms for these properties include inhibition of mTORC2 and Akt in prostate cancer cells, inhibition of HER2 expression in HER2-positive breast cancer cells, and immunomodulatory effects in melanoma cancer cells.9-11 Aloe-emodin also enhanced the effect of dabrafenib in BRAF-mutant melanoma cancer cells.11

In animal models, dietary aloe-emodin prevented CRC tumor development in an Apc-deficient mouse model and also reduced the number of CRC tumors in a colitis-related colon carcinogenesis model.12 Nude mice bearing orthotopic HER2-positive breast cancer cells demonstrated a decrease in tumor size and weight with aloe-emodin in a dose-dependent manner.10 Tumor tissue from these mice showed downregulation of HER2 overexpression with aloe-emodin treatment.

Emodin

Emodin has similarly been demonstrated to inhibit cancer cell proliferation, migration, and invasion, reduce cell viability, and induce cell cycle arrest and apoptosis.13-21 Some mechanisms that have been identified include promoting reactive oxygen species production and downregulating CXCR4 and VEGFR2 expression and STAT3 activation.16,22,13

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Many of the in vitro findings have been confirmed in animal models. Emodin inhibited the growth of orthotopic breast cancer tumors and attenuated metastasis and angiogenesis.14,15,23 Emodin also inhibited tumor growth in several studies of hepatocellular carcinoma, and oral and lung cancer.13,16,23,25 Some studies showed that emodin decreased angiogenesis or suppressed metastasis.16,22

Results have, however, been mixed in models of CRC. Though one study showed that emodin suppressed tumor growth in a xenograft model, another study found no significant difference in tumor growth.17,26 A study that treated rats with cascara for 13 weeks found no aberrant colonic crypt foci.27

Conclusions

Cascara use is not recommended because there are insufficient data for establishing its safety, and there have been reports of liver injury with high doses.28 It is, however, unlikely to cause colorectal adenomas or carcinomas. The cascara constituents, aloe-emodin and emodin, have anticancer properties in vitro and in animal models, and may therefore warrant additional studies in humans.

References

  1. van Gorkom BA, de Vries EG, Karrenbeld A, Kleibeuker JH. Review article: anthranoid laxatives and their potential carcinogenic effects. Aliment Pharmacol Ther. 1999;13:443-52.
  2. Food and Drug Administration, HHS. Status of certain additional over-the-counter drug category II and III active ingredients. Final rule. Fed Regist. 2002;67(90):31125-7.
  3. National Toxicology Program. NTP Toxicology and Carcinogenesis Studies of EMODIN (CAS NO. 518-82-1) Feed Studies in F344/N Rats and B6C3F1 Mice. Natl Toxicol Program Tech Rep Ser. 2001;493:1-278.
  4. Nusko G, Schneider B, Schneider I, Wittekind C, Hahn EG. Anthranoid laxative use is not a risk factor for colorectal neoplasia: results of a prospective case control study. Gut. 2000;46:651-5.
  5. Nascimbeni R, Donato F, Ghirardi M, Mariani P, Villanacci V, Salerni B. Constipation, anthranoid laxatives, melanosis coli, and colon cancer: a risk assessment using aberrant crypt foci. Cancer Epidemiol Biomark Prev. 2002;11:753-7.
  6. Citronberg J, Kantor ED, Potter JD, White E. A prospective study of bowel movement frequency, constipation, and laxative use on colorectal cancer risk. Am J Gastroenterol. 2014;109:1640-9. doi: 10.1038/ajg.2014.233
  7. Westendorf J. (1993) Anthranoid Derivatives — general discussion. In: De Smet PAGM, Keller K, Hänsel R, Chandler RF, eds. Adverse Effects of Herbal Drugs 2. Adverse Effects of Herbal Drugs 2. Germany: Springer; 1993:105-18. doi: 10.1007/978-3-642-48906-8_3
  8. Sanders B, Ray AM, Goldberg S, et al. Anti-cancer effects of aloe-emodin: A systematic review. J Clin Transl Res. 2017;3:283-96. doi: 10.18053/jctres.03.201703.001
  9. Liu K, Park C, Li S, et al. Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2. Carcinogenesis. 2012;33:1406-11.
  10. Ma JW, Hung CM, Lin YC, Ho CT, Kao JY, Way TD. Aloe-emodin inhibits HER-2 expression through the downregulation of Y-box binding protein-1 in HER-2-overexpressing human breast cancer cells. Oncotarget. 2016;7:58915-31.
  11. Tabolacci C, Cordella M, Turcano L, et al. Aloe-emodin exerts a potent anticancer and immunomodulatory activity on BRAF-mutated human melanoma cells. Eur J Pharmacol. 2015;762:283-92. doi: 10.1016/j.ejphar.2015.05.057
  12. Shimpo K, Chihara T, Kaneko T, et al. Inhibitory effects of low-dose aloe-emodin on the development of colorectal tumors in min mice. Asian Pac J Cancer Prev. 2014;15:5587-92. doi: 10.7314/APJCP.2014.15.14.5587
  13. Su J, Yan Y, Qu J, Xue X, Liu Z, Cai H. Emodin induces apoptosis of lung cancer cells through ER stress and the TRIB3/NF-κB pathway. Oncol Rep. 2017;37:1565-72. doi: 10.3892/or.2017.5428
  14. Sun Y, Wang X, Zhou Q, et al. Inhibitory effect of emodin on migration, invasion and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo. Oncol Rep. 2015;33:338-46. doi: 10.3892/or.2014.3585
  15. Ma J, Lu H, Wang S, et al. The anthraquinone derivative emodin inhibits angiogenesis and metastasis through downregulating Runx2 activity in breast cancer. Int J Oncol. 2015;46:1619-28. doi: 10.3892/ijo.2015.2888
  16. Lin W, Zhong M, Yin H, et al. Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo. Oncol Rep. 2016;36:961-7. doi: 10.3892/or.2016.4861
  17. Ma YS, Weng SW, Lin MW, et al. Antitumor effects of emodin on LS1034 human colon cancer cells in vitro and in vivo: roles of apoptotic cell death and LS1034 tumor xenografts model. Food Chem Toxicol. 2012;50:1271-8. doi: 10.1016/j.fct.2012.01.033
  18. Lee KH, Lee MS, Cha EY, et al. Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis. Oncol Rep. 2017;15:2163-73. doi: 10.3892/mmr.2017.6254
  19. Guo HC, Bu HQ, Luo J, et al. Emodin potentiates the antitumor effects of gemcitabine in PANC-1 pancreatic cancer xenograft model in vivo via inhibition of inhibitors of apoptosis. Int J Oncol. 2012;40:1849-57. doi: 10.3892/ijo.2012.1389
  20. Li X, Wang H, Wang J, et al. Emodin enhances cisplatin-induced cytotoxicity in human bladder cancer cells through ROS elevation and MRP1 downregulation. BMC Cancer. 2016;16:578-88. doi: 10.1186/s12885-016-2640-3
  21. Ma L, Yang Y, Yin Z, et al. Emodin suppresses the nasopharyngeal carcinoma cells by targeting the chloride channels. Biomed Pharmacother. 2017;90:615-25. doi: 10.1016/j.biopha.2017.03.088
  22. Manu KA, Shanmugam MK, Ong TH, et al. Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. PLoS ONE. 2015;8:e57015. doi: 10.1371/journal.pone.0057015
  23. Subramaniam A, Shanmugam MK, Ong TH, et al. Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3. Br J Pharmacol. 2013;170:807-21. doi: 10.1111/bph.12302
  24. Iwanowycz S, Wang J, Hodge J, Wang Y, Yu F, Fan D. Emodin inhibits breast cancer growth by blocking the tumor-promoting feedforward loop between cancer cells and macrophages. Mol Cancer Ther. 2016;15:1931-42. doi: 10.1158/1535-7163.MCT-15-0987
  25. Manimaran A, Manoharan S, Neelakandan M. Emodin efficacy on the AKT, MAPK, ERK and DNMT expression pattern during DMBA-induced oral carcinoma in golden Syrian hamsters. Afr J Tradit Comlement Altern Med. 2016;13:186-93. doi: 10.21010/ajtcam. v13i6.27
  26. Braumann C, Koplin G, Geier C, et al. Dose-dependent role of novel agents emodin and BTB14431 in colonic cancer treatment in rats. Acta Chir Belg. 2017;117:376-84. doi: 10.1080/00015458.2017.1341145
  27. Borrelli F, Mereto E, Capasso F, et al. Effect of bisacodyl and cascara on growth of aberrant crypt foci and malignant tumors in the rat colon. Life Sci. 2001;69:1871-7.
  28. Nakasone ES, Tokeshi J. A serendipitous find: a case of cholangiocarcinoma identified incidentally after acute liver injury due to cascara sagrada ingestion. Hawaii J Med Pub Health. 2015;74:200-3.

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