Journal of Cell Signaling
Open Access
ISSN: 2576-1471
ISSN: 2576-1471
Suchismita Raha and Gon Sup Kim
Gyeongsang National University, South Korea
Posters & Accepted Abstracts: J Cell Signal
mTOR pathway dysregulation plays a key role in various cancers. To date, mTOR is the most well characterized negative regulator of autophagy in cancer cells suggesting that the decrease of autophagic activity is related to tumorigenesis (Xie et al., 2013). Advances in lysosome research playing a crucial role in cellular degradation. Lysosomal membrane permeabilization (LMP) followed by the release of cathepsins to the cytosol is considered to be a key activation step for lysosomal death pathway (Kirkegaard and Jaattela, 2009). Lysosome positioning adds complexity to the mTOR/lysosome/autophagy axis. Mitochondrial swelling, the release of ROS give a feedback loop to the nearby lysosome, contributes to more cathepsin D release in cytosol due to the intralysosomal degradation and cytoskeletal disruption (Aits and Jaattela, 2013). Gastric cancer remains to be highly prevalent and accounts for a notable proportion of global cancer mortality deaths worldwide. Therefore, this study aimed to elucidate the underlying molecular mechanisms of how Naringin-induced autophagic cell death in AGS cancer cells. A significant decrease of PI3K/Akt/mTOR cascade; an increase of Beclin 1, LC3B, P21, cytosolic cathepsin D; activation of ERK1/2, P38 and JNK proteins expression was observed by western blot. Significant reactive oxygen species (ROS) generation observed at 9 and 12h using DCFDA by flow cytometer. Activation of mitochondria at 12h and lysosome at 6h was observed by the confocal image. At 12h Bcl-xL and pBad sensitizer, BH3 domain protein was significantly down-regulated. Rapamycin inhibits mTOR, enhances LC3B; bafilomycin A1 inhibits cathepsin D, autophago lysosome, and ROS. NAC inhibits ROS, pERK1/2, pp38, LC3B whereas, U0126 inhibits pERK1/2, LC3B; SB203580 inhibits pp38, both suppressions of LC3B was observed in confocal imaging. Significant differential identified proteome profile showed relevant protein-protein interaction with major nodes linked to cell death signal, cell growth regulator, a tumor suppressor, organelle transport and proteasomal degradation assuring the potential biomarker for AGS cells treatment against flavonoid. Thus these present findings demonstrated Naringin induced lysosome degradation and mitochondrial oxidative stress lead to autophagic cell death in AGS cancer cells suggesting a therapeutic target for gastric cancer treatment enhancement
Suchismita Raha, presently a post-doctoral fellow in the laboratory of Biochemistry on a focused area of cancer cell death and cell regulatory mechanism, Gyeongsang National University (GNU). She is an Indian and received her PhD degree from GNU on gastric cancer cell death mechanism, in 2014-2017 under the fund of National Research Foundation. She pursued her Bachelor’s degree from Central Agricultural University, 2007 and Master’s degree from Centre for Plant Molecular Biology, Tamil Nadu Agricultural University, 2009 as Indian Council for Agricultural Research (ICAR) fellow with a project entitled Marker-assisted introgression of the Sub1 locus in Rice. She later joined as a research assistant in Barwale Foundation, 2009-2010, Hyderabad, India in a project entitled Mapping of QTL linked to Bph gene in rice. She joined to ICAR NE complex as Research Associate and worked on Identification of drought-tolerant QTL in local cultivars of rice and introgression of QTL through marker-assisted approach, 2011-2013 She has received Young Scientific Pioneer Awards during her PhD program in 2015 and 2016. She has received excellent poster award in International Conference for Korean Society of Cellular and Molecular Biology, 2017.
E-mail: suchibiodash@gmail.com