Norditerpenoids from the Seeds of Podocarpus nagi as Cytotoxic Agents and Autophagy Inducers

UM > Institute of Chinese Medical Sciences

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	Norditerpenoids from the Seeds of Podocarpus nagi as Cytotoxic Agents and Autophagy Inducers
	Feng, Z.; Zhang, L.; Zheng, Y.; Liu, Q.; Liu, J.; Yao, S.; Ye, Y.; Lu, J.; Lin, L.
	2017-06-28
Source Publication	Natural Products in Health, Agro-Food and Cosmetics
Abstract	In searching for new anti-cancer natural products1,2, eleven new totarane-type norditerpenoids, 1-deoxy-2β-hydroxy-nagilactone A, 2-oxo-nagilactone A, 7β-hydroxy-nagilactone D, 3-epi-nagilactone D, nagilactones K and L, 3β-hydroxy-nagilactone L, 2β-hydroxy-nagilactone L, 3-epi-15-hydroxy-nagilactone D, 1α-chloro-2β,3β,15-trihydroxy-nagilactone L and 15-hydroxy-nagilactone L, were isolated from the seeds of Podocarpus nagi, along with six known ones. Their structures were established based on detailed NMR and HRESIMS analysis. The absolute configuration of 1-deoxy-2β-hydroxy-nagilactone A was further determined by single crystal X-ray diffraction. All the isolates were tested for cytotoxic activity on cancer cells. The results indicated that 1-deoxy-2β-hydroxy-nagilactone A, 3-epi-nagilactone D, nagilactones K and L, and 2β-hydroxy-nagilactone L displayed significant cytotoxicity against A2780 and HEY cancer cells. 2β-Hydroxy-nagilactone L showed the highest potential with IC50 of less than 2.5 μM on the two cell lines. Furthermore, 2β-hydroxy-nagilactone L induced autophagic flux in A2780 cells, as evidenced by enhanced expression level of the autophagy marker phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and increased mRFP-GFP-LC3 puncta. Meanwhile, 2β-hydroxy-nagilactone L activated c-Jun N-terminal kinase (JNK) pathway and pretreatment with the JNK inhibitor SP600125 decreased 2β-hydroxy-nagilactone L-induced autophagy. In summary, a series of norditerpenoids were identified from P. nagi with cytotoxic activity, and 2β-hydroxy-nagilactone L was identified as a novel autophagy inducer.
Keyword	Podocarpus nagi norditerpenoids cytotoxicity autophagy inducer
Language	英語English
The Source to Article	PB_Publication
PUB ID	30978
Document Type	Conference paper
Collection	Institute of Chinese Medical Sciences
Corresponding Author	Lu, J.; Lin, L.
Recommended Citation GB/T 7714	Feng, Z.,Zhang, L.,Zheng, Y.,et al. Norditerpenoids from the Seeds of Podocarpus nagi as Cytotoxic Agents and Autophagy Inducers[C], 2017.
APA	Feng, Z.., Zhang, L.., Zheng, Y.., Liu, Q.., Liu, J.., Yao, S.., Ye, Y.., Lu, J.., & Lin, L. (2017). Norditerpenoids from the Seeds of Podocarpus nagi as Cytotoxic Agents and Autophagy Inducers. Natural Products in Health, Agro-Food and Cosmetics.

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