Epolactaene, a Novel Neuritogenic Compound in Human Neuroblastoma Cells, Produced by a Marine Fungus.

Kakeya, Hideaki; Takahashi, Ikuo; Okada, Gen; Isono, Kiyoshi; Osada, Hiroyuki

doi:10.7164/antibiotics.48.733

Cited by 136 publications

(74 citation statements)

References 5 publications

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“…In previous studies, we discovered epolactaene, which has a g-lactam ring and an alkyl chain at the C-3 position, induced neurite outgrowth in SH-SY5Y cells (Kakeya et al, 1995). In this study, we found that one of our synthetic epolactaene derivatives, MT-21, which has a g-lactam ring and an alkyl chain at the N-1 position, induced apoptosis in human leukemia HL-60 cells.…”

Section: Discussionmentioning

confidence: 57%

Requirement of protein kinase (Krs/MST) activation for MT-21-induced apoptosis

1999

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Fas is a well characterized apoptosis-inducing factor. One of our synthetic compounds, MT-21, induced apoptosis in human leukemia HL-60 cells similar to Fas. MT-21 activated caspase-3, an important cysteine aspartic protease for apoptosis induction. MT-21 also activated c-Jun-NH 2 -terminal kinase (JNK), a member of mitogen activated protein kinase (MAPK) superfamily that is involved in the regulation of cell growth, di erentiation and cell death. Moreover, MT-21 treatment resulted in the activation of a 36 kDa kinase which uses myelin basic protein (MBP) as a substrate. However, MAPK and p38 were not activated by treatment with MT-21. The 36 kDa MBP kinase was shown to be a proteolytic product derived from the Krs protein with a molecular weight of 60 kDa. The Krs protein is a Ser/Thr protein kinase whose activity is enhanced by digestion of its C-terminal regulatory domain by caspase-3. When a kinase-inactive mutant form of Krs protein was overexpressed in HL-60 cells, JNK activation and apoptosis induction by MT-21 were suppressed. Furthermore, overexpression of dominant negative c-Jun also suppressed apoptosis induction by MT-21. These ®ndings indicate that MT-21 induces apoptosis by the activation of JNK via the Krs protein, which is activated by caspase cleavage.

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Section: Discussionmentioning

confidence: 57%

Requirement of protein kinase (Krs/MST) activation for MT-21-induced apoptosis

1999

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“…1,[8][9][10] They found that epolactaene bound to human Hsp60 and inhibited its chaperone activity. 9,10) Ikekita et al found that 1 induced apoptosis in a human leukemia B cell line, BALL-1.…”

Section: -7)mentioning

confidence: 99%

Synthetic and Structure-Activity Relationship Studies on Bioactive Natural Products

Kuramochi

2013

Bioscience, Biotechnology, and Biochemistry

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“…[137] and epolactaene, a polyene from a Penicillium sp. [138], induce the differentiation of neuronal cells and could be of interest for regeneration of nerve cells (Fig. 14).…”

Section: Agents With Other Indicationsmentioning

confidence: 99%