The Diarylheptanoid Hirsutenone Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin via Modulation of Apoptosis-inducing Factor and X-linked Inhibitor of Apoptosis

Farrand, Lee; Kim, Ji Young; Byun, Sun‐Sig; Im-Aram, Akechai; Lee, Jihoon; Suh, Jeong Yong; Lee, Ki Won; Lee, Hyong Joo; Tsang, Benjamin K.

doi:10.1074/jbc.m113.513879

Cited by 33 publications

(23 citation statements)

References 29 publications

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“…Diarylheptanoids are notable in the biomedical literature for their toxicity (Sati et al 2011) and promise for cancer treatments (Farrand et al 2014); some evidence also suggests diarylheptanoids inhibit digestion in herbivores (Sunnerheim and Bratt 2004). Diarylheptanoids are notable in the biomedical literature for their toxicity (Sati et al 2011) and promise for cancer treatments (Farrand et al 2014); some evidence also suggests diarylheptanoids inhibit digestion in herbivores (Sunnerheim and Bratt 2004).…”

mentioning

confidence: 99%

Intraspecific leaf chemistry drives locally accelerated ecosystem function in aquatic and terrestrial communities

Jackrel

Morton

Wootton

2016

Ecology

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Resource patchiness influences consumer foraging, movement, and physiology. Fluxes across ecosystem boundaries can extend these effects to otherwise distinct food webs. Intraspecific diversity of these cross-ecosystem subsidies can have large consequences for recipient systems. Here, we show intraspecific variation in leaf defensive chemistry of riparian trees drives local adaptation among terrestrial and riverine decomposers that consume shed leaf litter. We found extensive geographic structuring of ellagitannins, diarylheptanoids, and flavonoids in red alder trees. Ellagitannins, particularly those with strong oxidative activity, drive aquatic leaf decomposition. Further, spatial variation in these leaf components drives local ecological matching: in experiments using artificial food sources distinguished only by the chemical content of individual trees, we found decomposers both on land and in rivers more quickly consumed locally derived food sources. These results illustrate that terrestrial processes can change the chemistry of cross-ecosystem subsidies in ways that ultimately alter ecosystem function in donor and recipient systems.

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confidence: 99%

Intraspecific leaf chemistry drives locally accelerated ecosystem function in aquatic and terrestrial communities

Jackrel

Morton

Wootton

2016

Ecology

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“…In particular, the anti‐adipogenic activity of phytochemicals that inhibit PI3K activation have been widely investigated. HST is a highly potent inhibitor of PI3K kinase activity in vitro [Farrand et al, ].…”

Section: Discussionmentioning

confidence: 99%

Hirsutenone Directly Targets PI3K and ERK to Inhibit Adipogenesis in 3T3‐L1 Preadipocytes

Cheong

Suk

Thimmegowda

et al. 2015

J of Cellular Biochemistry

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Adipogenesis is a key driver of the expansion of adipose tissue mass that causes obesity. Hirsutenone (HST) is an active botanical diarylheptanoid present in Alnus species. In this study, we evaluated the effects of HST on adipogenesis, its mechanisms of action and the molecular targets involved. Using Oil Red O staining, we observed that HST dose-dependently suppresses lipid accumulation during adipogenesis in 3T3-L1 preadipocytes, concomitant with a decrease in peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid synthase (FAS) protein expression. This inhibitory effect was largely limited to the early stage of adipogenesis, which includes mitotic clonal expansion (MCE), as evidenced by delayed cell cycle entry of preadipocytes from G1 to S phase. Furthermore, the regulation of MCE was accompanied by suppression of phosphatidylinositol 3-kinase (PI3K) and extracellular-regulated kinase (ERK) activity. HST was also shown to bind directly to PI3K and ERK1 in a non-ATP competitive manner. Our results suggest that HST attenuates adipogenesis by directly targeting PI3K and ERK during MCE in 3T3-L1 preadipocytes, underscoring the potential therapeutic application of HST in preventing obesity.

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“…In chemo- and radiotherapy, similar signaling cascades are involved in the p53 activation of DNA damage, and the WT p53 gene plays an essential role in inducing apoptosis. It has been demonstrated that there were relevancies between the mutant p53 genes and resistance to chemotherapy in ovarian cancer [52], gastric and colorectal cancers [53], and in hematological malignancies [54]. In addition, dramatic differences were shown, indicating that the p53 status in tumors was not related to the chemotherapy response, but rather, that mutations in L2/L3 domains of the p53 gene in breast cancer were related to chemo-resistance [55].…”

Section: Clinical Issues and Experiences Of Gene Therapymentioning

confidence: 99%

Historical and Clinical Experiences of Gene Therapy for Solid Cancers in China

Gao

Zhang

et al. 2017

Genes

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Based on the theoretical and clinical development of modern medicines, gene therapy has been a promising treatment strategy for cancer and other diseases. The practice of gene therapy is nearly 27 years old, since the first authorized gene transfer study took place at the National Institute of Health in 1989. However, gene therapy was not readily adopted worldwide, until recently. Several gene therapy clinical trials have been carried out in China since 1998, and medical research in China has flourished. In this report, we review the history of gene therapy in China, focusing on treatment protocol, the administration cycle, dosage calculation, and the evaluation of therapeutic effects, in order to provide more information for the additional development of this promising treatment strategy.

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The Diarylheptanoid Hirsutenone Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin via Modulation of Apoptosis-inducing Factor and X-linked Inhibitor of Apoptosis

Cited by 33 publications

References 29 publications

Intraspecific leaf chemistry drives locally accelerated ecosystem function in aquatic and terrestrial communities

Intraspecific leaf chemistry drives locally accelerated ecosystem function in aquatic and terrestrial communities

Hirsutenone Directly Targets PI3K and ERK to Inhibit Adipogenesis in 3T3‐L1 Preadipocytes

Historical and Clinical Experiences of Gene Therapy for Solid Cancers in China

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