Abietane diterpenes from Abies spectabilis and their anti-pancreatic cancer activity against the MIA PaCa-2 cell line

Nguyen Duy Phan; Ashraf M. Omar; Sijia Sun; Juthamart Maneenet; Dya Fita Dibwe; Mao Sato; Surya Kant Kalauni; Naoki Toyooka; Tsutomu Fujii; Suresh Awale

doi:10.1016/j.bmcl.2022.128723

Abietane diterpenes from Abies spectabilis and their anti-pancreatic cancer activity against the MIA PaCa-2 cell line

Nguyen Duy Phan, Ashraf M. Omar, Sijia Sun, Juthamart Maneenet, Dya Fita Dibwe, Mao Sato, Surya Kant Kalauni, Naoki Toyooka, Tsutomu Fujii, Suresh Awale^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

An ethanolic extract of the stem of Abies spectabilis exhibited strong cytotoxicity against MIA PaCa-2 human pancreatic cancer cells preferentially under nutrient-deprived conditions. Therefore, phytochemical investigation of this bioactive extract was carried out, and that led the isolation of ten compounds (1–10) including a new abietane-type diterpene (1). The structure of the new compound (1) was elucidated by combined spectroscopic techniques, including HRFABMS, NMR and quantum ECD calculation. All the isolated compounds were evaluated for their efficacy against MIA PaCa-2 human pancreatic cancer cell line by employing an anti-austerity strategy. Among the tested compounds, dehydroabietinol (5) displayed the most potent activity with a PC₅₀ value of 6.6 μM. Dehydroabietinol (5) was also found to retard the MIA PaCa-2 cell migration under normal nutrient-rich conditions displaying its anti-metastatic potential. Investigation on the mechanism suggested that dehydroabietinol (5) is an inhibitor of the key cancer cell survival Akt/mTOR/autophagy signaling pathway.

Original language	English
Article number	128723
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	66
DOIs	https://doi.org/10.1016/j.bmcl.2022.128723
State	Published - 2022/06/15

Keywords

Abies spectabilis
Abietane
Diterpenes
MIA PaCa-2
Preferential cytotoxicity

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2022.128723

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@article{8eb950079bde499b8dbbf67cd452cb61,

title = "Abietane diterpenes from Abies spectabilis and their anti-pancreatic cancer activity against the MIA PaCa-2 cell line",

abstract = "An ethanolic extract of the stem of Abies spectabilis exhibited strong cytotoxicity against MIA PaCa-2 human pancreatic cancer cells preferentially under nutrient-deprived conditions. Therefore, phytochemical investigation of this bioactive extract was carried out, and that led the isolation of ten compounds (1–10) including a new abietane-type diterpene (1). The structure of the new compound (1) was elucidated by combined spectroscopic techniques, including HRFABMS, NMR and quantum ECD calculation. All the isolated compounds were evaluated for their efficacy against MIA PaCa-2 human pancreatic cancer cell line by employing an anti-austerity strategy. Among the tested compounds, dehydroabietinol (5) displayed the most potent activity with a PC50 value of 6.6 μM. Dehydroabietinol (5) was also found to retard the MIA PaCa-2 cell migration under normal nutrient-rich conditions displaying its anti-metastatic potential. Investigation on the mechanism suggested that dehydroabietinol (5) is an inhibitor of the key cancer cell survival Akt/mTOR/autophagy signaling pathway.",

keywords = "Abies spectabilis, Abietane, Diterpenes, MIA PaCa-2, Preferential cytotoxicity",

author = "Phan, {Nguyen Duy} and Omar, {Ashraf M.} and Sijia Sun and Juthamart Maneenet and Dibwe, {Dya Fita} and Mao Sato and Kalauni, {Surya Kant} and Naoki Toyooka and Tsutomu Fujii and Suresh Awale",

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",

year = "2022",

month = jun,

day = "15",

doi = "10.1016/j.bmcl.2022.128723",

language = "英語",

volume = "66",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

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TY - JOUR

T1 - Abietane diterpenes from Abies spectabilis and their anti-pancreatic cancer activity against the MIA PaCa-2 cell line

AU - Phan, Nguyen Duy

AU - Omar, Ashraf M.

AU - Sun, Sijia

AU - Maneenet, Juthamart

AU - Dibwe, Dya Fita

AU - Sato, Mao

AU - Kalauni, Surya Kant

AU - Toyooka, Naoki

AU - Fujii, Tsutomu

AU - Awale, Suresh

PY - 2022/6/15

Y1 - 2022/6/15

N2 - An ethanolic extract of the stem of Abies spectabilis exhibited strong cytotoxicity against MIA PaCa-2 human pancreatic cancer cells preferentially under nutrient-deprived conditions. Therefore, phytochemical investigation of this bioactive extract was carried out, and that led the isolation of ten compounds (1–10) including a new abietane-type diterpene (1). The structure of the new compound (1) was elucidated by combined spectroscopic techniques, including HRFABMS, NMR and quantum ECD calculation. All the isolated compounds were evaluated for their efficacy against MIA PaCa-2 human pancreatic cancer cell line by employing an anti-austerity strategy. Among the tested compounds, dehydroabietinol (5) displayed the most potent activity with a PC50 value of 6.6 μM. Dehydroabietinol (5) was also found to retard the MIA PaCa-2 cell migration under normal nutrient-rich conditions displaying its anti-metastatic potential. Investigation on the mechanism suggested that dehydroabietinol (5) is an inhibitor of the key cancer cell survival Akt/mTOR/autophagy signaling pathway.

AB - An ethanolic extract of the stem of Abies spectabilis exhibited strong cytotoxicity against MIA PaCa-2 human pancreatic cancer cells preferentially under nutrient-deprived conditions. Therefore, phytochemical investigation of this bioactive extract was carried out, and that led the isolation of ten compounds (1–10) including a new abietane-type diterpene (1). The structure of the new compound (1) was elucidated by combined spectroscopic techniques, including HRFABMS, NMR and quantum ECD calculation. All the isolated compounds were evaluated for their efficacy against MIA PaCa-2 human pancreatic cancer cell line by employing an anti-austerity strategy. Among the tested compounds, dehydroabietinol (5) displayed the most potent activity with a PC50 value of 6.6 μM. Dehydroabietinol (5) was also found to retard the MIA PaCa-2 cell migration under normal nutrient-rich conditions displaying its anti-metastatic potential. Investigation on the mechanism suggested that dehydroabietinol (5) is an inhibitor of the key cancer cell survival Akt/mTOR/autophagy signaling pathway.

KW - Abies spectabilis

KW - Abietane

KW - Diterpenes

KW - MIA PaCa-2

KW - Preferential cytotoxicity

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JO - Bioorganic and Medicinal Chemistry Letters

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M1 - 128723

ER -

Abietane diterpenes from Abies spectabilis and their anti-pancreatic cancer activity against the MIA PaCa-2 cell line

Abstract

Keywords

ASJC Scopus subject areas

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