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Baicalin Augments Hyperthermia-Induced Apoptosis In U937 Cells And Modulates The MAPK Pathway Via ROS Generation
S. A. Zakki, Zheng-Guo Cui, Lu Sun, Qian-Wen Feng, Meng-ling Li, H. Inadera
Published 2018 · Chemistry, Medicine
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Background/Aims: Hyperthermia is a widely used therapeutic tool for cancer therapy and a well-known inducer of apoptosis. Although the flavonoid compound baicalin (BCN) is a potent anticancer agent for several human carcinomas, it is less potent in the human U937 myelomonocytic leukemia cell line. To explore any enhancing effects of BCN on hyperthermia-induced apoptosis, this study investigated the combined effects and apoptotic mechanisms of hyperthermia and BCN in U937 cells. Methods: U937 cells were heat treated at 44ºC for 12 min with or without pre-treatment with BCN (10-50 µM) and then incubated for 6 h at 37 ºC with 5% CO2 and 95% air. Cell viability was analyzed by Trypan blue exclusion assay. Apoptosis was examined by DNA fragmentation, fluorescence microscopy and flow cytometry. Generation of mitochondrial trans-membrane potential (MMP), mitochondrial calcium, and reactive oxygen species (ROS) was also detected by flow cytometry. The expression of proteins related to apoptosis and signaling pathways was determined by western blotting. Results: Hyperthermia alone did not reduce cell viability or induce notable levels of apoptosis, but combined hyperthermia and BCN treatment markedly augmented apoptosis by upregulating proapoptotic proteins and suppressing antiapoptotic proteins, culminating in caspase-3 activation. Mitochondrial transmembrane potential was significantly decreased, and generation of reactive oxygen species (ROS) and suppression of antioxidant enzymes were marked. Furthermore, with the combined treatment, the phosphorylated forms of JNK and p38 showed increased expression, whereas AKT was dephosphorylated. JNK-IN-8 (a JNK inhibitor) and NAC (a ROS scavenger) abrogated the apoptotic effects of the combined treatment, significantly protecting the cells and indicating the involvement of high ROS generation and the MAPK pathway in the underlying molecular mechanism. Conclusion: This study provides compelling evidence that hyperthermia, in combination with BCN, is a promising therapeutic strategy for enhancement of apoptosis and suggest a promising therapeutic approach for cancer.
This paper references
Baicalin-induced apoptosis is mediated by Bcl-2-dependent, but not p53-dependent, pathway in human leukemia cell lines.
D. Shieh (2006)
Baicalin promoted site‐2 protease and not site‐1 protease in endoplasmic reticulum stress‐induced apoptosis of human hepatocellular carcinoma cells
Z. Yu (2016)
Mechanism of cell death induction by nitroxide and hyperthermia.
Q. Zhao (2006)
Autophagy and cancer.
Li Yen Mah (2012)
Molecular mechanisms of apoptosis and roles in cancer development and treatment.
S. Goldar (2015)
Flow cytometry as a quantitative
K Hertveldt (2006)
The effects of baicalein and baicalin on mitochondrial function and dynamics: A review.
M. R. de Oliveira (2015)
Targeting apoptosis pathways in cancer stem cells.
M. Signore (2013)
Hyperthermia: an effective strategy to induce apoptosis in cancer cells
Kanwal Ahmed (2015)
Scutellaria baicalensis, a herbal medicine: anti-proliferative and apoptotic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines.
T. Kumagai (2007)
Down-regulation of the PI3K/Akt signaling pathway and induction of apoptosis in CA46 Burkitt lymphoma cells by baicalin
Yi Huang (2012)
cancer development and treatment
M Signore (2015)
Placental endoplasmic reticulum stress in gestational diabetes: the potential for therapeutic intervention with chemical chaperones and antioxidants
Hong-wa Yung (2016)
Akt Phosphorylates and Negatively Regulates Apoptosis Signal-Regulating Kinase 1
A. Kim (2001)
Short-term hyperthermia promotes the sensitivity of MCF-7 human breast cancer cells to paclitaxel.
Yan Lin (2013)
G. L. Miller (2006)
Role of mitochondrial dysfunction and dysregulation of Ca2+ homeostasis in insulin insensitivity of mammalian cells
C. Wang (2015)
ROS-modulated therapeutic approaches in cancer treatment
M. H. Raza (2017)
Inhibitory effects of mild hyperthermia plus docetaxel therapy on ER(+/−) breast cancer cells and action mechanisms
F. Lv (2013)
Burkitt lymphoma cells by baicalin
Lu H-F (2012)
Sensitization of T cells to apoptosis—A role for ROS?
P. Tripathi (2004)
Apoptosis: Physiology and Pathology
J. C. Reed (2011)
Enhancement of apoptosis by nitric oxide released from alpha-phenyl-tert
Z-G Cui (2015)
Sensitization of T cells to
Apigenin Induces Apoptosis in Human Leukemia Cells and Exhibits Anti-Leukemic Activity In Vivo
A. Budhraja (2011)
The genus Epimedium: an ethnopharmacological and phytochemical review.
Huiping Ma (2011)
butyl nitrone under hyperthermic conditions
C Grootaert (2006)
Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin.
F. Chan (2000)
ROS mediates baicalin-induced apoptosis in human promyelocytic leukemia HL-60 cells through the expression of the Gadd153 and mitochondrial-dependent pathway.
Hsu-Fung Lu (2007)
Dephosphorylation and mitochondrial translocation of cofilin sensitizes human leukemia cells to cerulenin-induced apoptosis via the ROCK1/Akt/JNK signaling pathway
Yanhao Zhang (2016)
Differential roles of p38-MAPK and JNKs in mediating early protection or apoptosis in the hyperthermic perfused amphibian heart
C. Gaitanaki (2008)
The role of the Atg1/ULK1 complex in autophagy regulation.
N. Mizushima (2010)
Molecular mechanisms involved in the adaptive response to cadmium-induced apoptosis in human myelomonocytic lymphoma U937 cells.
Zheng-Guo Cui (2011)
Caspase-3 Is the Primary Activator of Apoptotic DNA Fragmentation via DNA Fragmentation Factor-45/Inhibitor of Caspase-activated DNase Inactivation*
Beni B Wolf (1999)
Flow Cytometric Method for the Detection of Flavonoids in Cell Lines
C. Grootaert (2016)
Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes.
K. Sellins (1987)
Flow cytometry as a quantitative and sensitive method to evaluate low dose radiation induced apoptosis in vitro in human peripheral blood lymphocytes.
K. Hertveldt (1997)
Scutellaria Baicalensis, a Herbal Medicine: Antitumor Activity Against Acute Lymphocytic Leukemia, Lymphoma and Myeloma in Vitro.
T. Kumagai (2004)
Regulation of Calcium Homeostasis by ER Redox: A Close-Up of the ER/Mitochondria Connection.
A. Chernorudskiy (2017)
The role of MAPK signalling pathways in the response to endoplasmic reticulum stress.
Nicola J. Darling (2014)
AKT serine/threonine protein kinase modulates baicalin-triggered autophagy in human bladder cancer T24 cells.
Chingju Lin (2013)
Anticancer Res 2007;27:117–125
The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase.
H. Yano (1994)
Molecular mechanisms of hyperthermia-induced apoptosis enhanced by withaferin A.
Zheng-Guo Cui (2014)
Use of Baicalin-Conjugated Gold Nanoparticles for Apoptotic Induction of Breast Cancer Cells
D. Lee (2016)
cervical cancer hela cells in-vitro. Iran
S Goldar (2015)
Baicalin induces apoptosis via mitochondrial pathway as prooxidant.
S. Ueda (2002)
The antitumour effects of eudesmin on lung cancer by inducing apoptosis via mitochondria-mediated pathway in the tumour cells
Li-li Jiang (2017)
Enhancement of apoptosis by nitric oxide released from α‐phenyl‐tert‐butyl nitrone under hyperthermic conditions
Zheng-Guo Cui (2006)
Effects and Mechanism of Baicalin on Apoptosis of Cervical Cancer HeLa Cells In-vitro
Y. Peng (2015)
Randomized trial of hyperthermia and radiation for superficial tumors.
E. Jones (2005)
Effects of hyperthermia as a mitigation strategy in DNA damage-based cancer therapies.
T. Mantso (2016)
Naringenin induces mitochondria-mediated apoptosis and endoplasmic reticulum stress by regulating MAPK and AKT signal transduction pathways in endometriosis cells
S. Park (2017)
The pro-survival function of Akt kinase can be overridden or altered to contribute to induction of apoptosis.
D. Benbrook (2011)
The Effect of Baicalin as A PPAR Activator on Erythroid Differentiation of CD133+Hematopoietic Stem Cells in Umbilical Cord Blood
P. Abbasi (2015)
Down-regulation of Mcl-1 by inhibition of the PI3-K/Akt pathway is required for cell shrinkage-dependent cell death.
T. Araki (2002)
Antioxidant and anticancer effects and bioavailability studies of the flavonoid baicalin and its oxidovanadium(IV) complex.
Juan J. Martínez Medina (2017)
Phenethyl isothiocyanate exhibits antileukemic activity in vitro and in vivo by inactivation of Akt and activation of JNK pathways
N. Gao (2011)
Mitogen-activated protein kinases in apoptosis regulation
T. Wada (2004)
Baicalin induces apoptosis in hepatic cancer cells in vitro and suppresses tumor growth in vivo.
Y. Yu (2015)
Author ' s
Nancy Argüelles (2008)
DNA damage-based cancer therapies. Semin Cancer Biol 2016;37–38:96–105
S Fu (2016)
In vitro antileukemic, antioxidant and prooxidant activities of Antoksyd S (C/E/XXI): a comparison with baicalin and baicalein.
E. Ciesielska (2004)
Molecular mechanisms of hyperthermia-induced apoptosis enhanced by docosahexaenoic acid: implication for cancer therapy.
Zheng-Guo Cui (2014)
Baicalin Scavenged Reactive Oxygen Species and Protected Human Keratinocytes Against UVB-induced Cytotoxicity.
Wen-Shin Chang (2016)
Baicalin suppresses NLRP3 inflammasome and nuclear factor-kappa B (NF-κB) signaling during Haemophilus parasuis infection
Shulin Fu (2016)
Selecting bioactive phenolic compounds as potential agents to inhibit proliferation and VEGF expression in human ovarian cancer cells
Zhiping He (2015)
Bardoxolone methyl (CDDO-Me or RTA402) induces cell cycle arrest, apoptosis and autophagy via PI3K/Akt/mTOR and p38 MAPK/Erk1/2 signaling pathways in K562 cells.
X. Wang (2017)
Vertical inhibition of the PI3K/Akt/mTOR pathway for the treatment of osteoarthritis
J. Chen (2013)
- a role for ROS ?
T Mantso (2004)
The role of Ca2+ in baicalein-induced apoptosis in human breast MDA-MB-231 cancer cells through mitochondria- and caspase-3-dependent pathway.
Jau-Hong Lee (2008)
Baicalin induces apoptosis
S Ueda (2015)
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Antitumor Activity In Vivo and Vitro of New Chiral Derivatives of Baicalin and Induced Apoptosis via the PI3K/Akt Signaling Pathway
Y. Hou (2020)
Epithelial ovarian cancer: feasibility of image-guided intratumoral radiofrequency hyperthermia-enhanced direct gene therapy.
G. Jin (2019)
Cinnamaldehyde and Hyperthermia Co-Treatment Synergistically Induces ROS-Mediated Apoptosis in ACHN Renal Cell Carcinoma Cells
Chae Ryeong Ahn (2020)
Baicalin attenuates myocardial ischemia‐reperfusion injury through Akt/NF‐κB pathway
Yun Luan (2019)
Usnea Acid as Multidrug Resistance (MDR) Reversing Agent against Human Chronic Myelogenous Leukemia K562/ADR Cells via an ROS Dependent Apoptosis
Wenjing Wang (2019)
Melatonin triggers the anticancer potential of phenylarsine oxide via induction of apoptosis through ROS generation and JNK activation.
S. A. Zakki (2020)
Kidney-targeted baicalin-lysozyme conjugate ameliorates renal fibrosis in rats with diabetic nephropathy induced by streptozotocin
Xiao-peng Zheng (2020)
Natural compounds modulate the crosstalk between apoptosis- and autophagy-regulated signaling pathways: Controlling the uncontrolled expansion of tumor cells.
C. Braicu (2020)
Combination Therapy with Cinnamaldehyde and Hyperthermia Induces Apoptosis of A549 Non-Small Cell Lung Carcinoma Cells via Regulation of Reactive Oxygen Species and Mitogen-Activated Protein Kinase Family
Jinbong Park (2020)