Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596640
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Antileukemic sesterterpenoids from a marine sponge, Luffariella sp.

KH Lai
1   Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
2   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
,
MC Lu
3   Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan
4   National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan
,
FR Chang
2   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
5   Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
6   Research Center for Natural Product and New Drug, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
,
JH Su
3   Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan
4   National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan
,
M El-Shazly
2   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
7   Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street, Abassia, Cairo 11566, Egypt
,
YC Du
2   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
,
TY Wu
2   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
,
YM Hsu
2   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
,
A Backlund
1   Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
,
YC Wu
2   Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
8   School of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan
9   Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 40447, Taiwan
10   Center for Molecular Medicine, China Medical University Hospital, Taichung 40447, Taiwan
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2016 (online)

Also available at
 
 

    Marine sponge of the genus Luffariella was found to be a rich source of novel cytotoxic and anti-inflammatory sesterterpenoids from previous reports [1, 2]. The further chemical investigation on this sponge led to the discovery of five new sesterterpenoids, luffarlides G-K, which were elucidated by spectroscopic methods including 1D and 2D NMR techniques. The absolute configurations were determined utilizing ECD/CD experiments. The antileukemic activity of the new compounds, along with the six previously described sesterterpenoids, were evaluated against Molt4 human acute lymphoblastic leukemic cell lines using MTT proliferative assay [3]. The most active compound, manoalide, was found to exhibit strong anti-proliferative activitie with IC50 values of 0.14 µg/mL. In addition, manoalide treatment activated caspase-related apoptotic proteins and mitogen-activated protein kinases (MAPK) of Molt4 cells with Western blot assay [3]. Analyzed by flow cytometry, manoalide treatment induced cancer cells apoptosis via disruption of mitochondrial membrane potential and generation of intracellular reactive oxygen species (ROS) in Molt4 cells. Manoalide could inhibit both activities of human topoisomerase I and II with gel electrophoresis [3]. DNA damage responses were directly detected with increase of H2AX phosphorylation, biomarker of DNA damage, and DNA break by comet assay. Importantly, the apoptosis-caused by manoalide could be recovered with NAC pretreatment, but not with pretreatments of caspase and MAPK inhibitors. Taken together, these results suggested that cytotoxic effect of manoalide is to mediate ROS generation, and finally resulted in cellular DNA damage and apoptosis. The findings provide support for further ChemGPS-NP targets investigation as well as the in vivo evaluation of lead compound.

    Keywords: Luffarilla sp., sesterterpenoids, manoalide, Molt4, ROS-mediated apoptosis, DNA damage.

    References:

    [1] Kernan MR, Faulkner DJ, Parkanyi L, Clardy J, Decarvalho MS, Jacobs RS. Luffolide, a novel anti-Inflammatory terpene from the sponge Luffariella sp. Experientia 1989; 45: 388 – 390

    [2] Zhou GX, Molinski TF. Manoalide derivatives from a sponge, Luffariella sp. J Asian Nat Prod Res, 2006; 8: 15 – 20

    [3] Shih SP, Lee MG, El-Shazly M, Juan YS, Wen ZH, Du YC, Su JH, Sung PJ, Chen YC, Yang JC, Wu YC, Lu MC. Tackling the cytotoxic effect of a marine polycyclic quinone-type metabolite: Halenaquinone induces molt 4 cells apoptosis via oxidative stress combined with the inhibition of HDAC and topoisomerase activities. Mar Drugs 2015; 13: 3132 – 3153


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    No conflict of interest has been declared by the author(s).