TY - JOUR
T1 - The citrus flavanone hesperetin induces apoptosis in ctcl cells via STAT3/Notch1/NFκB-mediated signaling axis
AU - Kottaiswamy, Amuthavalli
AU - Kizhakeyil, Atish
AU - Padmanaban, Abirami M.
AU - Mirza, Fathima B.
AU - Vijay, Venkatesh R.
AU - Lee, Pin S.
AU - Verma, Navin K.
AU - Kalaiselvan, Parkavi
AU - Samuel, Shila
N1 - Publisher Copyright:
© 2020 Bentham Science Publishers.
PY - 2020
Y1 - 2020
N2 - Background: Hesperetin is a natural compound known for its cholesterol-lowering effect and a wide range of pharmacological activities. Objectives: Investigating the potential anticancer activities of Hesperetin in malignant hematolymphoid cell lines HuT78 and MJ, derived from patients with Cutaneous T-Cell Lymphomas (CTCL). Methods: The cytotoxic effect of Hesperetin on two different CTCL cell lines, HuT78 and MJ, was assessed by MTS-based colorimetric assay. Apoptosis, cell cycle, ROS (Reactive Oxygen Species) and molecular analysis were performed using flow-cytometry and immunoblotting. Results: Hesperetin-treated CTCL cells were arrested at the sub-G1 phase of cell cycle with the concomitant decrease in the expression of the cell cycle regulator protein cyclin B. In addition, the study found that the cellular treatment with Hesperetin caused an induction of apoptosis, which was independent of ROS generation. Hesperetin caused a significant decrease in the expression level of anti-apoptotic protein Bcl-xL and an increase in cleaved caspase-3 and PARP proteins in CTCL cells. Furthermore, Hesperetin treatment in CTCL cells down-regulated the expression of Notch1 and phosphorylation of STAT3 (Tyr705) and inhibited NFκBp65. Conclusion: This study highlights the anticancer properties of Hesperetin. Which induces apoptosis in CTCL cells via STAT3/Notch1/NFκB mediated signaling pathway, suggesting that further development of this novel class of flavonoid may contribute to new drug discovery for certain hematolymphoid malignancies.
AB - Background: Hesperetin is a natural compound known for its cholesterol-lowering effect and a wide range of pharmacological activities. Objectives: Investigating the potential anticancer activities of Hesperetin in malignant hematolymphoid cell lines HuT78 and MJ, derived from patients with Cutaneous T-Cell Lymphomas (CTCL). Methods: The cytotoxic effect of Hesperetin on two different CTCL cell lines, HuT78 and MJ, was assessed by MTS-based colorimetric assay. Apoptosis, cell cycle, ROS (Reactive Oxygen Species) and molecular analysis were performed using flow-cytometry and immunoblotting. Results: Hesperetin-treated CTCL cells were arrested at the sub-G1 phase of cell cycle with the concomitant decrease in the expression of the cell cycle regulator protein cyclin B. In addition, the study found that the cellular treatment with Hesperetin caused an induction of apoptosis, which was independent of ROS generation. Hesperetin caused a significant decrease in the expression level of anti-apoptotic protein Bcl-xL and an increase in cleaved caspase-3 and PARP proteins in CTCL cells. Furthermore, Hesperetin treatment in CTCL cells down-regulated the expression of Notch1 and phosphorylation of STAT3 (Tyr705) and inhibited NFκBp65. Conclusion: This study highlights the anticancer properties of Hesperetin. Which induces apoptosis in CTCL cells via STAT3/Notch1/NFκB mediated signaling pathway, suggesting that further development of this novel class of flavonoid may contribute to new drug discovery for certain hematolymphoid malignancies.
KW - Apoptosis
KW - CTCL
KW - NFκB
KW - Notch1
KW - ROS
KW - STAT3
UR - http://www.scopus.com/inward/record.url?scp=85088025006&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088025006&partnerID=8YFLogxK
U2 - 10.2174/1871521409666200324110031
DO - 10.2174/1871521409666200324110031
M3 - Article
C2 - 32208126
AN - SCOPUS:85088025006
SN - 1871-5206
VL - 20
SP - 1459
EP - 1468
JO - Anti-Cancer Agents in Medicinal Chemistry
JF - Anti-Cancer Agents in Medicinal Chemistry
IS - 12
ER -
