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

Bioorg Med Chem Lett. 2022 Jun 15:66:128723. doi: 10.1016/j.bmcl.2022.128723. Epub 2022 Apr 6.

Authors

Affiliations

¹ Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.
² Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
³ Central Department of Chemistry, Kirtipur, Kathmandu, Nepal.
⁴ Faculty of Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan; Graduate School of Innovative Life Science, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan.
⁵ Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.
⁶ Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: suresh@inm.u-toyama.ac.jp.

PMID: 35395369
DOI: 10.1016/j.bmcl.2022.128723

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abies*
Abietanes / pharmacology
Antineoplastic Agents, Phytogenic* / chemistry
Cell Line, Tumor
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Pancreatic Neoplasms* / drug therapy
Pancreatic Neoplasms* / pathology
Plant Extracts / therapeutic use

Substances

Abietanes
Antineoplastic Agents, Phytogenic
Plant Extracts