TY - JOUR T1 - Novel Cytotoxic Isolated from Jamaican <em>Hyptis verticillata</em> jacq Induces Apoptosis and Overcomes Multidrug Resistance JF - Anticancer Research JO - Anticancer Res SP - 4251 LP - 4257 VL - 31 IS - 12 AU - YOHANN WHITE AU - TOSHIYUKI HAMADA AU - MAKOTO YOSHIMITSU AU - MITSUYOSHI NAKASHIMA AU - MIHO HACHIMAN AU - TOMOHIRO KOZAKO AU - KAKUSHI MATSUSHITA AU - KIMIHARU UOZUMI AU - SHINSUKE SUZUKI AU - HIROKI KOFUNE AU - TATSUHIKO FURUKAWA AU - NAOMICHI ARIMA Y1 - 2011/12/01 UR - http://ar.iiarjournals.org/content/31/12/4251.abstract N2 - 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 G2/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 G2/M arrest and apoptosis in cancer cells possibly due to direct DNA damage or interference with topoisomerase II. ER -