PMID- 24583240 OWN - NLM STAT- MEDLINE DCOM- 20150601 LR - 20140328 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 153 IP - 1 DP - 2014 Apr 11 TI - Anti-melanoma activity of Cynanchi atrati Radix is mediated by regulation of NF-kappa B activity and pro-apoptotic proteins. PG - 250-7 LID - S0378-8741(14)00150-0 [pii] LID - 10.1016/j.jep.2014.02.037 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchi atrati Radix has been traditionally prescribed for patients with inflammatory fever or chronic tumoral disorders. Melanoma is one of the most devastating cancer types, in which overexpression of nuclear factor kappa B (NF-kappaB) enables the cancer to survive without apoptosis. To identify a potential anti-melanoma candidate, we evaluated the apoptotic activity of an ethanol extract of Cynanchi atrati Radix (CAE) on melanoma and its underlying mechanisms. MATERIALS AND METHODS: Sixty C57BL/6N mice with melanoma were orally administrated CAE (100 or 200mg/kg) or distilled water for 10 days. Survival, tumor weight and volume were monitored and measured. Intratumoral apoptotic change was measured using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. To confirm the pro-apoptotic activity of CAE (10, 50 or 100mug/mL) compared to positive drug (10mug/mL of IKK-2 inhibitor IV), cell proliferation, caspase-3/7 activity, flow cytometric analysis, TUNEL and DAPI staining, immunoblotting and gene expression analyses for apoptosis-associated genes were conducted using B16F10 cell line. RESULTS: CAE administration remarkably improved survivability with a significant reduction in tumor weight (p<0.01) and volume (p<0.01), as well as increased apoptotic bodies in melanoma tissue. The CAE treatment significantly inhibited proliferation of B16F10 cells (p<0.001), but increased caspase-3/7 activity (p<0.01 or 0.001) and apoptotic population. The CAE partially blocked nuclear translocation of NF-kappaB but activated the p53-associated apoptotic pathway. CONCLUSION: These results indicate that the CAE has anti-melanoma potential, and the underlying mechanisms involve inhibition of the activities of NF-kappaB and its target proteins as well as promoting the activities of pro-apoptotic proteins. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Son, Seung-Wan AU - Son SW AD - Department of Biomedical Engineering, College of Health Science, Korea University, Seongbuk-Gu, Seoul 136-703, Republic of Korea. FAU - Kim, Hyeong-Geug AU - Kim HG AD - Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea. FAU - Han, Jong-Min AU - Han JM AD - Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea. FAU - Lee, Jin-Seok AU - Lee JS AD - Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea. FAU - Choi, Min-Kyung AU - Choi MK AD - Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea. FAU - Lee, Jong-Seok AU - Lee JS AD - Gyeonggi Biocenter, Gyeonggi Institute of Science & Technology Promotion (GSTEP), Suwon, Gyeonggi-do 443-270, Republic of Korea. FAU - Son, Chang-Gue AU - Son CG AD - Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea. Electronic address: ckson@dju.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140226 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) SB - IM MH - Animals MH - Antineoplastic Agents, Phytogenic/administration & dosage/isolation & purification/*pharmacology MH - Apoptosis/drug effects MH - Apoptosis Regulatory Proteins/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cynanchum/*chemistry MH - Dose-Response Relationship, Drug MH - Flow Cytometry MH - Gene Expression Regulation, Neoplastic/drug effects MH - In Situ Nick-End Labeling MH - Male MH - Melanoma, Experimental/*drug therapy/pathology MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/metabolism MH - Plant Extracts/administration & dosage/*pharmacology MH - Plant Roots MH - Skin Neoplasms/drug therapy/pathology OTO - NOTNLM OT - Apoptosis OT - B16F10 OT - Cynanchi Atrati Radix OT - Melanoma OT - Nuclear factor kappa B EDAT- 2014/03/04 06:00 MHDA- 2015/06/02 06:00 CRDT- 2014/03/04 06:00 PHST- 2013/10/28 00:00 [received] PHST- 2014/02/16 00:00 [revised] PHST- 2014/02/17 00:00 [accepted] PHST- 2014/03/04 06:00 [entrez] PHST- 2014/03/04 06:00 [pubmed] PHST- 2015/06/02 06:00 [medline] AID - S0378-8741(14)00150-0 [pii] AID - 10.1016/j.jep.2014.02.037 [doi] PST - ppublish SO - J Ethnopharmacol. 2014 Apr 11;153(1):250-7. doi: 10.1016/j.jep.2014.02.037. Epub 2014 Feb 26.