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Novel Cytotoxic Isolated from Jamaican Hyptis verticillata jacq Induces Apoptosis and Overcomes Multidrug Resistance.
MedLine Citation:
PMID:  22199288     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND: Adult T-cell leukemia is an aggressive hematological malignancy with a poor clinical prognosis, and a rapid resistance to chemotherapy is rapid.
MATERIALS AND METHODS: Cytotoxicity assay-directed fractionation identified a novel lignan-related agent, 4-methoxy-9-(3,4,5-trimethoxyphenyl)-8, 9 - dihydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5H)-one (4-MTDND) from the Jamaican plant Hyptis verticillata jacq, and its effects on apoptosis, cell cycle and drug resistance were elucidated.
RESULTS: The novel agent, 4-MTDND, exhibited cytotoxicity against myriad cancer types, with a wide therapeutic index of 30- to 40-fold, promoted G(2)/M arrest and up-regulated expression of pro-apoptotic proteins p53 and BAX, as well as enhanced activation of caspase-3, caspase-9 and poly (ADP ribose) polymerase, consistent with apoptosis induction. Multidrug-resistant cancer cells were as susceptible to 4-MTDND as their non-resistant control counterparts, with 4-MTDND having greater efficacy compared to standard chemotherapy agents etoposide and mitoxantrone.
CONCLUSION: The novel cytotoxic agent 4-MTDND induces G(2)/M arrest and apoptosis in cancer cells possibly due to direct DNA damage or interference with topoisomerase II.
Yohann White; Toshiyuki Hamada; Makoto Yoshimitsu; Mitsuyoshi Nakashima; Miho Hachiman; Tomohiro Kozako; Kakushi Matsushita; Kimiharu Uozumi; Shinsuke Suzuki; Hiroki Kofune; Tatsuhiko Furukawa; Naomichi Arima
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  31     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  4251-7     Citation Subset:  IM    
Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan.
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