Disruption of Endoplasmic Reticulum and ROS Production in Human Ovarian Cancer by Campesterol

Phytosterols, which are present in a variety of foods, exhibit various physiological functions and do not have any side effects. Here, we attempted to identify functional role of campesterol in regulation of oxidative stress by leading to cell death of ovarian cancer. We investigated the effects of campesterol on cancer cell aggregation using a three-dimensional (3D) culture of human ovarian cancer cells. The effects of campesterol on apoptosis, protein expression, proliferation, the cell cycle, and the migration of these cells were determined to unravel the underlying mechanism. We also investigated whether campesterol regulates mitochondrial function, the generation of reactive oxygen species (ROS), and calcium concentrations. Our results show that campesterol activates cell death signals and cell death in human ovarian cancer cells. Excessive calcium levels and ROS production were induced by campesterol in the two selected ovarian cancer cell lines. Moreover, campesterol suppressed cell proliferation, cell cycle progression, and cell aggregation in ovarian cancer cells. Campesterol also enhanced the anticancer effects of conventional anticancer agents. The present study shows that campesterol can be used as a novel anticancer drug for human ovarian cancer.

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Gomisin L1, a Lignan Isolated from Schisandra Berries, Induces Apoptosis by Regulating NADPH Oxidase in Human Ovarian Cancer Cells

Life ◽

10.3390/life11080858 ◽

2021 ◽

Vol 11 (8) ◽

pp. 858

Author(s):

Young Hyun Ko ◽

Miran Jeong ◽

Dae Sik Jang ◽

Jung-Hye Choi

Keyword(s):

Ovarian Cancer ◽

Cell Death ◽

Nadph Oxidase ◽

Cancer Cells ◽

Apoptotic Cell ◽

Biological Activities ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Ros Production ◽

Food Ingredients

The fruits of Schisandra chinensis (Schisandra berries) are used as health food supplements and popular food ingredients in East Asia. Lignans, major and characteristic polyphenol compounds of Schisandra berries, possess various biological activities, including hepatoprotective and anticancer effects. However, the biological activities of gomisin L1, a lignan isolated from Schisandra berries, are less to be investigated. In this study, the antitumor activity of gomisin L1 and its underlying molecular mechanism in human ovarian cancer cells were investigated. Gomisin L1 exhibited potent cytotoxic activity against A2780 and SKOV3 ovarian cancer cells. Flow cytometry analysis revealed that the growth inhibitory effects of gomisin L1 were mediated by the induction of apoptosis. Furthermore, gomisin L1 induced an increase in intracellular reactive oxygen species (ROS) levels, and the antioxidant N-acetyl cysteine significantly negated gomisin L1-induced cell death. Moreover, inhibition of NADPH oxidase (NOX) using an inhibitor and siRNA attenuated gomisin L1-induced death of, and ROS production in, human ovarian cancer cells. Taken together, these data indicate that the lignan gomisin L1 from Schisandra berries induces apoptotic cell death by regulating intracellular ROS production via NOX.

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Adenosine Analogues as Opposite Modulators of the Cisplatin Resistance of Ovarian Cancer Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190118113201 ◽

2019 ◽

Vol 19 (4) ◽

pp. 473-486 ◽

Cited By ~ 1

Author(s):

Katarzyna Bednarska-Szczepaniak ◽

Damian Krzyżanowski ◽

Magdalena Klink ◽

Marek Nowak

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Biology ◽

Immune Cell ◽

Immunosuppressive Agents ◽

Cell Activity ◽

Ovarian Cancer Cells ◽

Adenosine Analogues

Background: Adenosine released by cancer cells in high amounts in the tumour microenvironment is one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive and cisplatin-resistant ovarian cancer cells to cisplatin treatment. Methods: The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/ antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis events and cisplatin incorporation in cancer cells were determined. Results: PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring mitochondrial and plasma membrane potentials that were disturbed by cisplatin. Conclusion: Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell biology should be considered in the context of supportive chemotherapy for ovarian cancer.

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CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion

Cancers ◽

10.3390/cancers13112745 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2745

Author(s):

Miran Jeong ◽

Yi-Yue Wang ◽

Ju-Yeon Choi ◽

Myong-Cheol Lim ◽

Jung-Hye Choi

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Invasion ◽

Ovarian Cancer Cell ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Cancer Cell Invasion ◽

Cc Chemokine ◽

Chemokine Ligand

In the tumor microenvironment, macrophages have been suggested to be stimulated by tumor cells, becoming tumor-associated macrophages that promote cancer development and progression. We examined the effect of these macrophages on human ovarian cancer cell invasion and found that conditioned medium of macrophages stimulated by ovarian cancer cells (OC-MQs) significantly increased cell invasion. CC chemokine ligand 7 (CCL7) expression and production were significantly higher in OC-MQs than in the control macrophages. Peritoneal macrophages from patients with ovarian cancer showed higher CCL7 expression levels than those from healthy controls. Inhibition of CCL7 using siRNA and neutralizing antibodies reduced the OC-MQ-CM-induced ovarian cancer cell invasion. CC chemokine receptor 3 (CCR3) was highly expressed in human ovarian cancer cells, and a specific inhibitor of this receptor reduced the OC-MQ-CM-induced invasion. Specific signaling and transcription factors were associated with enhanced CCL7 expression in OC-MQs. CCL7-induced invasion required the expression of matrix metalloproteinase 9 via activation of extracellular signal-related kinase signaling in human ovarian cancer cells. These data suggest that tumor-associated macrophages can affect human ovarian cancer metastasis via the CCL7/CCR3 axis.

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VCP inhibitors induce endoplasmic reticulum stress, cause cell cycle arrest, trigger caspase-mediated cell death and synergistically kill ovarian cancer cells in combination with Salubrinal

Molecular Oncology ◽

10.1016/j.molonc.2016.09.005 ◽

2016 ◽

Vol 10 (10) ◽

pp. 1559-1574 ◽

Cited By ~ 30

Author(s):

Prabhakar Bastola ◽

Lisa Neums ◽

Frank J. Schoenen ◽

Jeremy Chien

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Endoplasmic Reticulum ◽

Cell Death ◽

Endoplasmic Reticulum Stress ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Induce Endoplasmic Reticulum Stress ◽

Cycle Arrest

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Honokiol and Magnolol Induce Apoptosis and Cell Cycle Arrest in Human Ovarian Cancer Cells

Pharmacognosy Journal ◽

10.5530/pj.2019.11.174 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1114-1123

Author(s):

Worawat Songjang ◽

Arunya Jiraviriyakul

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Cycle Arrest

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Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells

Molecules ◽

10.3390/molecules25010207 ◽

2020 ◽

Vol 25 (1) ◽

pp. 207 ◽

Cited By ~ 2

Author(s):

Yi-Yue Wang ◽

Jun Hyeok Kwak ◽

Kyung-Tae Lee ◽

Tsegaye Deyou ◽

Young Pyo Jang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Death ◽

Cancer Cells ◽

Caspase 3 ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Millettia Ferruginea ◽

Induced Apoptosis

The seeds of Millettia ferruginea are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from M. ferruginea were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3’,4’-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.

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