Searching for a New Anti‐Cancer Drug: Investigation of KY Hemp‐Induced Apoptosis in Ovarian Cancer Cells

In addition to their analgesic activity, transient receptor potential vanilloid 1 (TRPV1) agonists and antagonists demonstrate profound anti-cancer activities in various human cancers. In the present study, we investigated the anti-cancer activity of a novel TRPV1 antagonist, DWP05195, and evaluated its molecular mechanism in human ovarian cancer cells. DWP05195 demonstrated potent growth inhibitory effects in all five ovarian cancer cell lines examined. DWP05195 induced apoptosis through the activation of caspase-3, -8, and -9. DWP05195 induced C/EBP homologous protein (CHOP) expression and endoplasmic reticulum (ER) stress. Sodium phenylbutyrate (4-PBA), an ER-stress inhibitor, and CHOP knockdown significantly suppressed DWP5195-induced cell death. DWP05195-enhanced CHOP expression stimulated intrinsic and extrinsic apoptotic pathways through the regulation of Bcl2-like11 (BIM), death receptor 4 (DR4), and DR5. DWP05195-induced cell death was associated with increased reactive oxygen species (ROS) levels and p38 pathway activation. Pre-treatment with the antioxidant N-acetyl-L-cysteine (NAC) significantly suppressed DWP05195-induced CHOP expression and p38 activation. Inhibition of NADPH oxidase (NOX) through p47phox knockdown abolished DWP05195-induced CHOP expression and cell death. Taken together, the findings indicate that DWP05195 induces ER stress-induced apoptosis via the ROS-p38-CHOP pathway in human ovarian cancer cells.

Download Full-text

Differences in cisplatin distribution in sensitive and resistant ovarian cancer cells: a TEM/NanoSIMS study

Metallomics ◽

10.1039/c7mt00153c ◽

2017 ◽

Vol 9 (10) ◽

pp. 1413-1420 ◽

Cited By ~ 18

Author(s):

Ronald F. S. Lee ◽

Tina Riedel ◽

Stéphane Escrig ◽

Catherine Maclachlan ◽

Graham W. Knott ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Acquired Resistance ◽

Cancer Drug ◽

Ovarian Cancer Cells ◽

Anti Cancer

Cisplatin is a widely used anti-cancer drug, but its effect is often limited by acquired resistance to the compound during treatment.

Download Full-text

High expression of crystallin αB represents an independent molecular marker for unfavourable ovarian cancer patient outcome and impairs TRAIL- and cisplatin-induced apoptosis in human ovarian cancer cells

International Journal of Cancer ◽

10.1002/ijc.27975 ◽

2012 ◽

Vol 132 (12) ◽

pp. 2820-2832 ◽

Cited By ~ 21

Author(s):

Juliane Volkmann ◽

Ute Reuning ◽

Martina Rudelius ◽

Norman Häfner ◽

Tibor Schuster ◽

...

Keyword(s):

Patient Outcome ◽

Ovarian Cancer ◽

Molecular Marker ◽

Cancer Patient ◽

Cancer Cells ◽

Ovarian Cancer Patient ◽

High Expression ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Induced Apoptosis

Download Full-text

Galangin, a Flavonoid from Lesser Galangal, Induced Apoptosis via p53-Dependent Pathway in Ovarian Cancer Cells

Molecules ◽

10.3390/molecules25071579 ◽

2020 ◽

Vol 25 (7) ◽

pp. 1579 ◽

Cited By ~ 4

Author(s):

Haizhi Huang ◽

Allen Y. Chen ◽

Xingqian Ye ◽

Rongfa Guan ◽

Gary O. Rankin ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Regulatory Protein ◽

Ovarian Cancer Cells ◽

Apoptotic Pathway ◽

Bax Protein ◽

Platinum Based Chemotherapy ◽

Phosphorylated Akt ◽

Induced Apoptosis

Among women worldwide, ovarian cancer is one of the most dangerous cancers. Patients undergoing platinum-based chemotherapy might get adverse side effects and develop resistance to drugs. In recent years, natural compounds have aroused growing attention in cancer treatment. Galangin inhibited the growth of two cell lines, A2780/CP70 and OVCAR-3, more strongly than the growth of a normal ovarian cell line, IOSE 364. The IC50 values of galangin on proliferation of A2780/CP70, OVCAR-3 and IOSE 364 cells were 42.3, 34.5, and 131.3 μM, respectively. Flow cytometry analysis indicated that galangin preferentially induced apoptosis in both ovarian cancer cells with respect to normal ovarian cells. Galangin treatment increased the level of cleaved caspase-3 and -7 via the p53-dependent intrinsic apoptotic pathway by up-regulating Bax protein and via the p53-dependent extrinsic apoptotic pathway by up-regulating DR5 protein. By down-regulating the level of p53 with 20 μM pifithrin-α (PFT-α), the apoptotic rates of OVCAR-3 cells induced by galangin treatment (40 μM) were significantly decreased from 18.2% to 10.2%, indicating that p53 is a key regulatory protein in galangin-induced apoptosis in ovarian cancer cells. Although galangin up-regulated the expression of p21, it had little effect on the cell cycle of the two ovarian cancer cell lines. Furthermore, the levels of phosphorylated Akt and phosphorylated p70S6K were decreased through galangin treatment, suggesting that the Akt/p70S6K pathways might be involved in the apoptosis. Our results suggested that galangin is selective against cancer cells and can be used for the treatment of platinum-resistant ovarian cancers in humans.

Download Full-text

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.

Download Full-text

Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

Tumor Biology ◽

10.1177/1010428317694302 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769430 ◽

Cited By ~ 10

Author(s):

Zhenhua Du ◽

Xianqun Sha

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Natural Form ◽

Ovarian Cancer Cell Lines ◽

Induced Apoptosis ◽

Tumor Suppressive Function ◽

Cancer Tissues

Curcumin is a natural agent that has ability to dampen tumor cells’ growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells’ malignant progress via up-regulating miR-551a.

Download Full-text