Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells

Plant-derived conjugated linolenic acids (CLnA) have been widely studied for their preventive and therapeutic properties against diverse diseases such as cancer. In particular, punicic acid (PunA), a conjugated linolenic acid isomer (C18:3 c9t11c13) present at up to 83% in pomegranate seed oil, has been shown to exert anti-cancer effects, although the mechanism behind its cytotoxicity remains unclear. Ferroptosis, a cell death triggered by an overwhelming accumulation of lipid peroxides, has recently arisen as a potential mechanism underlying CLnA cytotoxicity. In the present study, we show that PunA is highly cytotoxic to HCT-116 colorectal and FaDu hypopharyngeal carcinoma cells grown either in monolayers or as three-dimensional spheroids. Moreover, our data indicate that PunA triggers ferroptosis in carcinoma cells. It induces significant lipid peroxidation and its effects are prevented by the addition of ferroptosis inhibitors. A combination with docosahexaenoic acid (DHA), a known polyunsaturated fatty acid with anticancer properties, synergistically increases PunA cytotoxicity. Our findings highlight the potential of using PunA as a ferroptosis-sensitizing phytochemical for the prevention and treatment of cancer.

Download Full-text

A 3D Cell Death Assay to Quantitatively Determine Ferroptosis in Spheroids

Cells ◽

10.3390/cells9030703 ◽

2020 ◽

Vol 9 (3) ◽

pp. 703 ◽

Cited By ~ 5

Author(s):

Robin Demuynck ◽

Iuliia Efimova ◽

Abraham Lin ◽

Heidi Declercq ◽

Dmitri V. Krysko

Keyword(s):

Cell Death ◽

Three Dimensional ◽

Drug Efficacy ◽

Cost Effective ◽

3D Cultures ◽

Cell Death Assay ◽

Tumour Spheroids ◽

A Cell ◽

Triton X

The failure of drug efficacy in clinical trials remains a big issue in cancer research. This is largely due to the limitations of two-dimensional (2D) cell cultures, the most used tool in drug screening. Nowadays, three-dimensional (3D) cultures, including spheroids, are acknowledged to be a better model of the in vivo environment, but detailed cell death assays for 3D cultures (including those for ferroptosis) are scarce. In this work, we show that a new cell death analysis method, named 3D Cell Death Assay (3DELTA), can efficiently determine different cell death types including ferroptosis and quantitatively assess cell death in tumour spheroids. Our method uses Sytox dyes as a cell death marker and Triton X-100, which efficiently permeabilizes all cells in spheroids, was used to establish 100% cell death. After optimization of Sytox concentration, Triton X-100 concentration and timing, we showed that the 3DELTA method was able to detect signals from all cells without the need to disaggregate spheroids. Moreover, in this work we demonstrated that 2D experiments cannot be extrapolated to 3D cultures as 3D cultures are less sensitive to cell death induction. In conclusion, 3DELTA is a more cost-effective way to identify and measure cell death type in 3D cultures, including spheroids.

Download Full-text

Momordica charantiaExtract Induces Apoptosis in Human Cancer Cells through Caspase- and Mitochondria-Dependent Pathways

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/261971 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 19

Author(s):

Chia-Jung Li ◽

Shih-Fang Tsang ◽

Chun-Hao Tsai ◽

Hsin-Yi Tsai ◽

Jong-Ho Chyuan ◽

...

Keyword(s):

Cell Death ◽

Cytotoxic Activity ◽

Cancer Cells ◽

Dna Fragmentation ◽

Human Cancer ◽

Momordica Charantia ◽

Carcinoma Cells ◽

Human Cancer Cells ◽

Adenocarcinoma Cells ◽

Anti Cancer

Plants are an invaluable source of potential new anti-cancer drugs.Momordica charantiais one of these plants with both edible and medical value and reported to exhibit anticancer activity. To explore the potential effectiveness ofMomordica charantia, methanol extract ofMomordica charantia(MCME) was used to evaluate the cytotoxic activity on four human cancer cell lines, Hone-1 nasopharyngeal carcinoma cells, AGS gastric adenocarcinoma cells, HCT-116 colorectal carcinoma cells, and CL1-0 lung adenocarcinoma cells, in this study. MCME showed cytotoxic activity towards all cancer cells tested, with the approximate IC50ranging from 0.25 to 0.35 mg/mL at 24 h. MCME induced cell death was found to be time-dependent in these cells. Apoptosis was demonstrated by DAPI staining and DNA fragmentation analysis using agarose gel electrophoresis. MCME activated caspase-3 and enhanced the cleavage of downstream DFF45 and PARP, subsequently leading to DNA fragmentation and nuclear condensation. The apoptogenic protein, Bax, was increased, whereas Bcl-2 was decreased after treating for 24 h in all cancer cells, indicating the involvement of mitochondrial pathway in MCME-induced cell death. These findings indicate that MCME has cytotoxic effects on human cancer cells and exhibits promising anti-cancer activity by triggering apoptosis through the regulation of caspases and mitochondria.

Download Full-text

Abietane diterpenoid of Salvia sahendica Boiss and Buhse potently inhibits MCF-7 breast carcinoma cells by suppression of the PI3K/AKT pathway

RSC Advances ◽

10.1039/c4ra14905j ◽

2015 ◽

Vol 5 (23) ◽

pp. 18041-18050 ◽

Cited By ~ 15

Author(s):

Vala Kafil ◽

Morteza Eskandani ◽

Yadollah Omidi ◽

Hossein Nazemiyeh ◽

Jaleh Barar

Keyword(s):

Cell Death ◽

Breast Carcinoma ◽

Cell Lines ◽

Carcinoma Cells ◽

Akt Pathway ◽

Breast Carcinoma Cells ◽

Breast Cell Lines ◽

Anti Cancer ◽

Cancer Activity ◽

Mcf 7

Ketoethiopinone and ortho-diacetate aethiopinone were identified from the roots of S. sahendica and evaluated for their anti-cancer activity in MCF-7 breast cell lines. The type of cell death and the mechanism by which MCF-7 proliferation was limited were investigated.

Download Full-text

Blockade of irradiation-induced autophagosome formation impairs proliferation but does not enhance cell death in HCT-116 human colorectal carcinoma cells

International Journal of Oncology ◽

10.3892/ijo.2012.1329 ◽

2012 ◽

Vol 40 (4) ◽

pp. 1267-1276 ◽

Cited By ~ 2

Author(s):

ANA CRISTINA DE ALBUQUERQUE-XAVIER ◽

LILIAN GONÇALVES R. BASTOS ◽

JULIO CESAR MADUREIRA DE FREITAS ◽

FERNANDA LEVE ◽

WALDEMIR FERNÁNDEZ DE SOUZA ◽

...

Keyword(s):

Cell Death ◽

Colorectal Carcinoma ◽

Carcinoma Cells ◽

Autophagosome Formation ◽

Hct 116 ◽

Human Colorectal Carcinoma

Download Full-text

ID2010 Cytotoxicity of aqueous and ethanolic bark extracts of Pithecellobium dulce against human carcinoma cells

Biomedical Research and Therapy ◽

10.15419/bmrat.v4is.253 ◽

2017 ◽

Vol 4 (S) ◽

pp. 44

Author(s):

Shella Mae Jalique

Keyword(s):

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Line ◽

Carcinoma Cells ◽

Anticancer Activities ◽

Human Carcinoma ◽

Human Cancer Cell Lines ◽

Anticancer Properties ◽

Hct 116 ◽

Ethanol Extracts

Cancer cases continue to increase and kill humans. In this paper, we report a study based on anticancer properties of the aqueous and ethanolic bark extracts of Pithecellobium dulce. Anticancer activities were assayed with standard MTT colorimetric procedure against three human cancer cell lines namely breast (MCF-7), colon (HCT-116), and hepatocellular (HepG2) in different concentrations. The aqueous extract of the plant revealed the highest toxicity on hepatocellular carcinoma (HepG2) cancer cell line with cell viability of 1.71 percent. On the other hand, its ethanol extracts has the highest toxicity on colon carcinoma (HCT-116) with a percent viability of 6.05 percent. Based on the results, the bark of the plant can be used to prepare anticancer drug with proper standardization methods

Download Full-text

Analysis of Sensitivity and Cell Death Pathways Mediated by Anti-cancer Drugs Using Three-dimensional Culture System

International Journal of Cancer Research ◽

10.3923/ijcr.2018.1.12 ◽

2017 ◽

Vol 14 (1) ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Takeshi Kinoshita ◽

Hajime Higuchi ◽

Ayano- Kabashima- ◽

Gen Sakai ◽

Yasuo Hamamoto ◽

...

Keyword(s):

Cell Death ◽

Culture System ◽

Three Dimensional ◽

Cancer Drugs ◽

Cell Death Pathways ◽

Anti Cancer ◽

Three Dimensional Culture

Download Full-text

An Aptamer Bio-barCode (ABC) assay using SPR, RNase H, and probes with RNA and gold-nanorods for anti-cancer drug screening

The Analyst ◽

10.1039/c7an01026e ◽

2017 ◽

Vol 142 (19) ◽

pp. 3579-3587 ◽

Cited By ~ 13

Author(s):

Jacky Fong-Chuen Loo ◽

Chengbin Yang ◽

Hing Lun Tsang ◽

Pui Man Lau ◽

Ken-Tye Yong ◽

...

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Gold Nanorods ◽

Drug Screening ◽

Rnase H ◽

Cancer Drug ◽

Next Generation ◽

Anti Cancer ◽

A Cell

We have developed a next generation aptamer-based bio-barcode (ABC) assay to detect cytochrome-c (Cyto-c), a cell death marker released from cancer cells, for anti-cancer drug screening.

Download Full-text

CJK-7, a Novel Flavonoid from Paulownia tomentosa Triggers Cell Death Cascades in HCT-116 Human Colon Carcinoma Cells via Redox Signaling

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666171026170009 ◽

2018 ◽

Vol 18 (3) ◽

pp. 428-437 ◽

Cited By ~ 6

Author(s):

Mahendra Pal Singh ◽

Ki Hun Park ◽

Tejinder Pal Khaket ◽

Sun Chul Kang

Keyword(s):

Colon Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Cancer Cells ◽

Human Colon ◽

Carcinoma Cells ◽

Paulownia Tomentosa ◽

Colon Carcinoma Cells ◽

Human Colon Carcinoma ◽

Hct 116

Background: Colon cancer is the second most common cancer to cause death worldwide. About half of colon cancers patients require adjuvant therapy to control relapse following surgical resection. Therefore, abolition of tumor cell progression using an effective chemotherapeutic agent holds a feasible approach to treat patients suffering from colon cancer. In the present study, we evaluated the effects of geranylated flavonoid CJK-7, isolated from Paulownia tomentosa on HCT-116 human colon carcinoma cells. Materials and Methods: The effects of CJK-7 as an active component on HCT-116 cells programmed cell death and its underlying molecular mechanism were examined by using MTT assay, morphological assessment, H2DCFDA staining, Fura-2AM staining, Hoechst-33342 staining, comet assay, Acridine orange staining, mitochondrial membrane potential (ΔΨm) assay and Western blot analyses. Results and Conclusion: The results revealed that, CJK-7 was capable of inducing caspase-dependent cell death events in cancer cells. Moreover, it was involved in up-regulation of autophagy signaling as evidenced by enhanced expression of LC3I/II. We also noticed stimulated expression of endoplasmic reticulum stress markers and phosphorylation of c-Jun NH2-terminal kinase (JNK), which was associated with up-regulated expression of p53, PUMA, Atg5 and Beclin-1, and down-regulation of Bcl-2, stressing the interaction of ROS on the aforementioned signaling. Furthermore, exposure to ROS scavengers (N-acetyl-l-cysteine (NAC), and JNK-specific inhibitor SP600125) significantly reversed the effects of CJK-7 by down-regulating apoptosis and autophagy signatures in HCT-116 cancer cells. Collectively our findings clarify the ROS-dependent regulatory effect of CJK-7 on programmed cell death signaling events in HCT-116 cancer cells while depicting its virile pro-oxidant capacity.

Download Full-text