To The Editor
The recent article by Ok et al. provided highly stimulating readingCitation1. Emodin may decrease growth in a number of systemic tumors besides prostate carcinomas.
Similar effects are seen in pancreatic malignancies. Emodin mediates this role by attenuating intra-tumoral angiogenesisCitation2. At the same time, it attenuates NF-κB activity and thereby augments intra-tumoral apoptosis. Emodin also tends to decrease eNOS phosphorylation. Simultaneously, tumor cell metastasis is also significantly decreased. These effects have been seen both in vivo and in vitro. Akt activation is also significantly decreased while the Bax/Bcl-2 ratio is typically increased. Caspase-9 activity is augmented at the same time. MMP-2 and MMP-9 expression is also decreased secondary to the administration of emodinCitation3. Interestingly, emodin increases the sensitivity of pancreatic cancers to other chemotherapeutic agents such as gemcitabine. It mediates this role by decreasing Bcl-2 expressionCitation4. At the same time, the dual combination results in marked increase of Bax expression resulting in accentuated apoptosis within the tumor.
Similar effects are also seen in colon carcinomas. Emodin administration results in G2/M phase arrest. Emodin mediates this role by activation of caspase-6Citation5. Simultaneous inhibition of cyclin B1 is seen while the Bax/Bcl-2 ratio is typically increasedCitation6. Caspase-9 activation accompanies the above changes and leads to further apoptosis. ROS production is also accentuated markedly. Typically, RhoB expression is decreased at the same timeCitation7. Similarly, MMP-2 activity is also attenuated. Inhibition of nuclear translocation of NF-κB accompanies the above changes. Emodin also inhibits growth in non-small cell lung carcinomas. It mediates this effect by decreasing Rad 51 expressionCitation8. These effects are dose dependent. ERCC1 expression is also decreased.
The above examples clearly show that emodin has significant anti-neoplastic activity.
References
- Ok S, Kim SM, Kim C, et al. Emodin inhibits invasion and migration of prostate and lung cancer cells by downregulating the expression of chemokine receptor CXCR4. Immunopharmacol Immunotoxicol 2012;34:768–78
- Lin SZ, Wei WT, Chen H, et al. Antitumor activity of emodin against pancreatic cancer depends on its dual role: promotion of apoptosis and suppression of angiogenesis. PLoS One 2012;7:e42146
- Liu A, Sha L, Shen Y, et al. Experimental study on anti-metastasis effect of emodin on human pancreatic cancer. Zhongguo Zhong Yao Za Zhi 2011;36:3167–71
- Liu A, Luo J, Zhang JH. Emodin combined gemcitabine inhibited the growth of pancreatic cancer in vitro and in vivo and its mechanisms study. Zhongguo Zhong Xi Yi Jie He Za Zhi 2012;32:652–6
- Suboj P, Babykutty S, Srinivas P, Gopala S. Aloe emodin induces G2/M cell cycle arrest and apoptosis via activation of caspase-6 in human colon cancer cells. Pharmacology 2012;89:91–8
- 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
- Suboj P, Babykutty S, Valiyaparambil Gopi DR, et al. Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-kappaB. Eur J Pharm Sci 2012;45:581–91
- He L, Bi JJ, Guo Q, et al. Effects of emodin extracted from Chinese herbs on proliferation of non-small cell lung cancer and underlying mechanisms. Asian Pac J Cancer Prev 2012;13:1505–10