Understanding The Effects Of Garcinia Atroviridis Essential Oils In Combination With 2-Deoxy-D-Glucose On Pancreatic Cancer Cells (Panc 1)
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Date
2020-12
Authors
Aziz, Fatin Athirah Abdul
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Pancreatic cancer is among the highest lethal cancer in the world and current
treatment and biomarker for this cancer is still limited. This study aimed to investigate
the anti-proliferative effects of essential oils extracted from the leaves (EO-L) and stem
bark (EO-B) of Garcinia atroviridis against human pancreatic cancer cell line, PANC-
1. The selective index (SI) values of each treatment was determined based on the ratio
of IC50 in BEAS-2B cells in comparison to PANC-1 cells. In PANC-1 cells, IC50 and
SI values of EO-L was 78 μg/ml and 1.23, respectively. EO-L at 100 μg/ml
concentration had induced 73.97% the release of LDH after 24 h of incubation period.
On the contrary, EO-B showed no pronounced anti-proliferative effect. Combination
treatment between EO-L and 2-DG showed moderate synergism, with combination
index (CI) values of 0.36 to 0.75. The effects of EO-L, 2-DG and EOL+2DG were
further investigated on mitochondrial membrane potential (MMP), apoptosis, cell
cycle and mRNA expression of selected regulatory molecules involved in apoptosis
and cellular metabolism. EO-L had induced 57.9% MMP and 49.7% apoptosis in
PANC-1 cells after 24 h of treatment. At 72 h of treatment, 2-DG and EOL+2DG
caused 47.6% and 60.8% of MMP, respectively. Both 2-DG and EOL+2DG had
caused PANC-1 cells to undergo apoptosis by 18.1% and 63.1%, respectively. Further,
EO-L had induced 24.5% accumulation of cells at S phase after 48 h of treatment. At
24 h treatment, 2-DG and EOL+2DG had induced PANC-1 cells to be accumulated at
G1 phase by 60.77% and 70.9%, respectively. EO-L had insignificant result in modulation of P53, HIF-1α, HK2 and CYP3A5 gene expression. 2-DG had
significantly decreased the expression of HK2 by 0.45-fold difference and increased
the expression of CYP3A5 by 44.7-fold difference relative to control cells. EOL+2DG
had significantly increased the expression of P53 gene by 1.5-fold difference
compared to control cells. Altogether, this study demonstrates the potential of EO-L
from G. atroviridis in inhibiting the growth of PANC-1 cells through its actions by
increasing the release of LDH, MMP, apoptosis and cell cycle arrest at S phase,
despite no significant result in the mRNA expression of P53, HIFα, HK2 and CYP3A5.
EO-L was found to synergize the actions of 2-DG in promoting cell death of PANC-1
cells.
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Keywords
Cancer