Chemical Constituents of <i>Callistemon subulatus</i> and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell Line

An n-hexane extract of <i>Callistemon subulatus</i> was found to exhibit potent cytotoxicity against PANC-1 human pancreatic cancer cells, preferentially under nutrition starvation conditions, with a PC<sub>50</sub> value of 6.2 µg/mL. Phytochemical investigation of this bioa...

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Main Authors: Juthamart Maneenet, Ahmed M. Tawila, Ashraf M. Omar, Nguyen Duy Phan, Chiharu Ojima, Masahiro Kuroda, Mao Sato, Mio Mizoguchi, Ikue Takahashi, Suresh Awale
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Plants
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Online Access:https://www.mdpi.com/2223-7747/11/19/2466
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author Juthamart Maneenet
Ahmed M. Tawila
Ashraf M. Omar
Nguyen Duy Phan
Chiharu Ojima
Masahiro Kuroda
Mao Sato
Mio Mizoguchi
Ikue Takahashi
Suresh Awale
author_facet Juthamart Maneenet
Ahmed M. Tawila
Ashraf M. Omar
Nguyen Duy Phan
Chiharu Ojima
Masahiro Kuroda
Mao Sato
Mio Mizoguchi
Ikue Takahashi
Suresh Awale
author_sort Juthamart Maneenet
collection DOAJ
description An n-hexane extract of <i>Callistemon subulatus</i> was found to exhibit potent cytotoxicity against PANC-1 human pancreatic cancer cells, preferentially under nutrition starvation conditions, with a PC<sub>50</sub> value of 6.2 µg/mL. Phytochemical investigation of this bioactive extract resulted in the isolation of fifteen compounds (<b>1</b>–<b>15</b>), including a new compound, subulatone A (–). The structure of compound <b>1</b> was elucidated using HRFABMS and NMR spectroscopic analyses. The isolated compounds were tested for their preferential cytotoxicity against the PANC-1 human pancreatic cancer cell line, using an anti-austerity strategy. Among these, myrtucommulone A (<b>2</b>) showed highly potent preferential cytotoxicity, with a PC<sub>50</sub> value of 0.28 µM. Myrtucommulone A (<b>2</b>) was found to alter PANC-1 cell morphology, inhibit cell migration, and downregulate the PI3K/Akt/mTOR and autophagy signaling pathways in nutrient-deprived media, leading to cancer cell death. Therefore, myrtucommulone A (<b>2</b>) is a lead compound for anticancer drug development based on an anti-austerity strategy.
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spelling doaj.art-da229ed3f9094358b1186c2fe088a1f52023-11-23T21:27:58ZengMDPI AGPlants2223-77472022-09-011119246610.3390/plants11192466Chemical Constituents of <i>Callistemon subulatus</i> and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell LineJuthamart Maneenet0Ahmed M. Tawila1Ashraf M. Omar2Nguyen Duy Phan3Chiharu Ojima4Masahiro Kuroda5Mao Sato6Mio Mizoguchi7Ikue Takahashi8Suresh Awale9Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanNatural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanNatural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanNatural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanNatural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanNatural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanNatural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanNatural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanNatural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanNatural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, JapanAn n-hexane extract of <i>Callistemon subulatus</i> was found to exhibit potent cytotoxicity against PANC-1 human pancreatic cancer cells, preferentially under nutrition starvation conditions, with a PC<sub>50</sub> value of 6.2 µg/mL. Phytochemical investigation of this bioactive extract resulted in the isolation of fifteen compounds (<b>1</b>–<b>15</b>), including a new compound, subulatone A (–). The structure of compound <b>1</b> was elucidated using HRFABMS and NMR spectroscopic analyses. The isolated compounds were tested for their preferential cytotoxicity against the PANC-1 human pancreatic cancer cell line, using an anti-austerity strategy. Among these, myrtucommulone A (<b>2</b>) showed highly potent preferential cytotoxicity, with a PC<sub>50</sub> value of 0.28 µM. Myrtucommulone A (<b>2</b>) was found to alter PANC-1 cell morphology, inhibit cell migration, and downregulate the PI3K/Akt/mTOR and autophagy signaling pathways in nutrient-deprived media, leading to cancer cell death. Therefore, myrtucommulone A (<b>2</b>) is a lead compound for anticancer drug development based on an anti-austerity strategy.https://www.mdpi.com/2223-7747/11/19/2466preferential cytotoxicitypancreatic canceranti-austerity<i>Callistemon subulatus</i>
spellingShingle Juthamart Maneenet
Ahmed M. Tawila
Ashraf M. Omar
Nguyen Duy Phan
Chiharu Ojima
Masahiro Kuroda
Mao Sato
Mio Mizoguchi
Ikue Takahashi
Suresh Awale
Chemical Constituents of <i>Callistemon subulatus</i> and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell Line
Plants
preferential cytotoxicity
pancreatic cancer
anti-austerity
<i>Callistemon subulatus</i>
title Chemical Constituents of <i>Callistemon subulatus</i> and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell Line
title_full Chemical Constituents of <i>Callistemon subulatus</i> and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell Line
title_fullStr Chemical Constituents of <i>Callistemon subulatus</i> and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell Line
title_full_unstemmed Chemical Constituents of <i>Callistemon subulatus</i> and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell Line
title_short Chemical Constituents of <i>Callistemon subulatus</i> and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell Line
title_sort chemical constituents of i callistemon subulatus i and their anti pancreatic cancer activity against human panc 1 cell line
topic preferential cytotoxicity
pancreatic cancer
anti-austerity
<i>Callistemon subulatus</i>
url https://www.mdpi.com/2223-7747/11/19/2466
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