The Ethanolic Extract of<i>Taiwanofungus camphoratus</i>(<i>Antrodia camphorata</i>) Induces Cell Cycle Arrest and Enhances Cytotoxicity of Cisplatin and Doxorubicin on Human Hepatocellular Carcinoma Cells

Lin, Liang-Tzung; Tai, Chen Jei; Su, Ching‐Hua; Chang, Fang Mo; Choong, Chen Yen; Wang, Chia-Woei; Tai, Ching Tai

doi:10.1155/2015/415269

Cited by 12 publications

(9 citation statements)

References 32 publications

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“…It has been shown that depletion of this subtype protects mice from DXR induced heart failure 29,30. Hence, cellular sensitivity would be important in chemotherapy and responsible for all drug administration programs in treating millions of people worldwide.…”

Section: Introductionmentioning

confidence: 99%

Monitoring the effects of doxorubicin on 3D-spheroid tumor cells in real-time

Baek¹,

Seo²,

Kim³

et al. 2016

OTT

116

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Recently, increasing numbers of cell culture experiments with 3D spheroids presented better correlating results in vivo than traditional 2D cell culture systems. 3D spheroids could offer a simple and highly reproducible model that would exhibit many characteristics of natural tissue, such as the production of extracellular matrix. In this paper numerous cell lines were screened and selected depending on their ability to form and maintain a spherical shape. The effects of increasing concentrations of doxorubicin (DXR) on the integrity and viability of the selected spheroids were then measured at regular intervals and in real-time. In total 12 cell lines, adenocarcinomic alveolar basal epithelial (A549), muscle (C2C12), prostate (DU145), testis (F9), pituitary epithelial-like (GH3), cervical cancer (HeLa), HeLa contaminant (HEp2), embryo (NIH3T3), embryo (PA317), neuroblastoma (SH-SY5Y), osteosarcoma U2OS, and embryonic kidney cells (293T), were screened. Out of the 12, 8 cell lines, NIH3T3, C2C12, 293T, SH-SY5Y, A549, HeLa, PA317, and U2OS formed regular spheroids and the effects of DXR on these structures were measured at regular intervals. Finally, 5 cell lines, A549, HeLa, SH-SY5Y, U2OS, and 293T, were selected for real-time monitoring and the effects of DXR treatment on their behavior were continuously recorded for 5 days. A potential correlation regarding the effects of DXR on spheroid viability and ATP production was measured on days 1, 3, and 5. Cytotoxicity of DXR seemed to occur after endocytosis, since the cellular activities and ATP productions were still viable after 1 day of the treatment in all spheroids, except SH-SY5Y. Both cellular activity and ATP production were halted 3 and 5 days from the start of the treatment in all spheroids. All cell lines maintained their spheroid shape, except SHSY-5, which behaved in an unpredictable manner when exposed to toxic concentrations of DXR. Cytotoxic effects of DXR towards SH-SY5Y seemed to cause degradation of the extracellular matrix, since all cells were dismantled from the spheroid upon cell death. On the other hand, 293T spheroids revealed retarded cellular activity and ATP productions upon DXR treatment throughout the experiment. Since 293T was the embryonic kidney cells, the fast clearance or neutralizations could have made them resistant towards DXR. In conclusion, the same degree of sensitivity from the 2D system did not translate to a 3D culture system, resulting in higher IC50 values than the 2D system. The varying sensitivities and tolerances to drugs could be better understood with a 3D cell culture system.

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Section: Introductionmentioning

confidence: 99%

Monitoring the effects of doxorubicin on 3D-spheroid tumor cells in real-time

Baek¹,

Seo²,

Kim³

et al. 2016

OTT

116

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“… 13 Previous studies reported that cancer cell lines Hep3B, HepJ5, ES-2, SKOV-3, OVCAR-3, and MCF-7 suffered a significant loss in cell viability upon CDDP treatment in 2D cultures. 9 , 14 – 16 Contrary to 2D cultures, when uterus/endometrium cell lines, such as Ishikawa, RL95-2, KLE, and the colon carcinoma cell line HCT116 were used to assess the effect of CDDP, no significant loss of viability was observed in 3D systems. 17 , 18 Instead, cell viability was greatly reduced upon CDDP treatment of 3D bone osteosarcoma cell lines (Saos-2, HOS).…”

Section: Introductionmentioning

confidence: 99%

Real-time monitoring of cisplatin cytotoxicity on three-dimensional spheroid tumor cells

Baek¹,

Seo²,

Lee³

et al. 2016

DDDT

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Three-dimensional (3D) cell cultivation is a powerful technique for monitoring and understanding diverse cellular mechanisms in developmental cancer and neuronal biology, tissue engineering, and drug development. 3D systems could relate better to in vivo models than two-dimensional (2D) cultures. Several factors, such as cell type, survival rate, proliferation rate, and gene and protein expression patterns, determine whether a particular cell line can be adapted to a 3D system. The 3D system may overcome some of the limitations of 2D cultures in terms of cell–cell communication and cell networks, which are essential for understanding differentiation, structural organization, shape, and extended connections with other cells or organs. Here, the effect of the anticancer drug cisplatin, also known as cis-diamminedichloroplatinum (II) or CDDP, on adenosine triphosphate (ATP) generation was investigated using 3D spheroid-forming cells and real-time monitoring for 7 days. First, 12 cell lines were screened for their ability to form 3D spheroids: prostate (DU145), testis (F9), embryonic fibroblast (NIH-3T3), muscle (C2C12), embryonic kidney (293T), neuroblastoma (SH-SY5Y), adenocarcinomic alveolar basal epithelial cell (A549), cervical cancer (HeLa), HeLa contaminant (HEp2), pituitary epithelial-like cell (GH3), embryonic cell (PA317), and osteosarcoma (U-2OS) cells. Of these, eight cell lines were selected: NIH-3T3, C2C12, 293T, SH-SY5Y, A549, HeLa, PA317, and U-2OS; and five underwent real-time monitoring of CDDP cytotoxicity: HeLa, A549, 293T, SH-SY5Y, and U-2OS. ATP generation was blocked 1 day after addition of 50 μM CDDP, but cytotoxicity in HeLa, A549, SH-SY5Y, and U-2OS cells could be visualized only 4 days after treatment. In 293T cells, CDDP failed to kill entirely the culture and ATP generation was only partially blocked after 1 day. This suggests potential CDDP resistance of 293T cells or metabolic clearance of the drug. Real-time monitoring and ATP measurements directly confirmed the cytotoxicity of CDDP, indicating that CDDP may interfere with mitochondrial activity.

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“…To minimize the disadvantages of cisplatin treatment, identifying novel anticancer agents that may kill cancerous cells with minimal toxicity is critical. Recent studies have demonstrated that some chemicals derived from herbal extracts possess antineoplastic effects (20,21), which were reported to arrest the progression of the cell cycle and to induce apoptotic cell death (22). Similarly, it has been presented by many studies that curcumin is one of the tumor suppressors that induces cell cycle arrest and apoptosis in a variety of cancer cells (23,24).…”

Section: Discussionmentioning

confidence: 99%

Curcumin analog EF24 induces apoptosis and downregulates the mitogen activated protein kinase/extracellular signal-regulated signaling pathway in oral squamous cell carcinoma

Chen¹,

Tu²,

Ma³

et al. 2017

Molecular Medicine Reports

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Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Diphenyldifluoroketone (EF24) is a curcumin analog that has been demonstrated to improve anticancer activity; however, its therapeutic potential and mechanisms in oral cancer remain unknown. In the present study, the effect of EF24 on apoptosis induction and its potential underlying mechanism in the CAL‑27 human OSCC cell line was investigated. To achieve this, various concentrations of cisplatin or EF24 were administrated to CAL‑27 cells for 24 h, and cell viability, apoptotic DNA fragmentation, and cleaved caspase 3 and 9 levels were evaluated. To investigate the potential underlying mechanism, the levels of mitogen‑activated protein kinase kinase 1 (MEK1) and extracellular signal‑regulated kinase (ERK), two key proteins in the mitogen‑activated protein kinase/ERK signaling pathway, were additionally examined. The results indicated that EF24 and cisplatin treatment decreased cell viability. EF24 treatment increased the levels of activated caspase 3 and 9, and decreased the phosphorylated forms of MEK1 and ERK. Sequential treatments of EF24 and 12‑phorbol‑13‑myristate acetate, a MAPK/ERK activator, resulted in a significant increase of activated MEK1 and ERK, and reversed cell viability. These results suggested that EF24 has potent anti‑tumor activity in OSCC via deactivation of the MAPK/ERK signaling pathway. Further analyses using animal models are required to confirm these findings in vivo.

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The Ethanolic Extract ofTaiwanofungus camphoratus(Antrodia camphorata) Induces Cell Cycle Arrest and Enhances Cytotoxicity of Cisplatin and Doxorubicin on Human Hepatocellular Carcinoma Cells

Cited by 12 publications

References 32 publications

Monitoring the effects of doxorubicin on 3D-spheroid tumor cells in real-time

Monitoring the effects of doxorubicin on 3D-spheroid tumor cells in real-time

Real-time monitoring of cisplatin cytotoxicity on three-dimensional spheroid tumor cells

Curcumin analog EF24 induces apoptosis and downregulates the mitogen activated protein kinase/extracellular signal-regulated signaling pathway in oral squamous cell carcinoma

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