Limits...
Autophagic Cell Death by Poncirus trifoliata Rafin., a Traditional Oriental Medicine, in Human Oral Cancer HSC-4 Cells.

Han HY, Park BS, Lee GS, Jeong SH, Kim H, Ryu MH - Evid Based Complement Alternat Med (2015)

Bottom Line: The methanol extract of P. trifoliata (MEPT) significantly decreased the proliferation of HSC-4 cells (inhibitory concentration (IC)50 = 142.7 μg/mL) in a dose-dependent manner.While there were no significant changes observed upon cell cycle analysis and ANNEXIN V and 7-AAD double staining in the MEPT-treated groups, the intensity of acidic vesicular organelle (AVO) staining and microtubule-associated protein 1 light chain (LC) 3-II protein expression increased in response to MEPT treatment.Taken together, our results indicate that MEPT is a potent autophagy agonist in oral cancer cells with antitumor therapeutic potential that acts through the mitogen-activated protein kinase (MAPK) pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Pathology, School of Dentistry, Institute of Translational Dental Sciences, Pusan National University, Yangsan, Republic of Korea.

ABSTRACT
Poncirus trifoliata Rafin. has long been used as anti-inflammatory and antiallergic agent to treat gastrointestinal disorders and pulmonary diseases such as indigestion, constipation, chest fullness, chest pain, bronchitis, and sputum in Korea. P. trifoliata extract has recently been reported to possess anticancer properties; however, its mechanisms of action remain unclear. In this study, its antiproliferative effects and possible mechanisms were investigated in HSC-4 cells. The methanol extract of P. trifoliata (MEPT) significantly decreased the proliferation of HSC-4 cells (inhibitory concentration (IC)50 = 142.7 μg/mL) in a dose-dependent manner. While there were no significant changes observed upon cell cycle analysis and ANNEXIN V and 7-AAD double staining in the MEPT-treated groups, the intensity of acidic vesicular organelle (AVO) staining and microtubule-associated protein 1 light chain (LC) 3-II protein expression increased in response to MEPT treatment. Furthermore, 3-methyladenine (3-MA, autophagy inhibitor) effectively blocked the MEPT-induced cytotoxicity of HSC-4 cells and triggered the activation of p38 and extracellular signal-regulated kinases (ERK) proteins. Taken together, our results indicate that MEPT is a potent autophagy agonist in oral cancer cells with antitumor therapeutic potential that acts through the mitogen-activated protein kinase (MAPK) pathway.

No MeSH data available.


Related in: MedlinePlus

MEPT-induced inhibition of proliferation and changes in cell morphology. HSC-4 cells treated with 0, 25, 50, 100, or 200 μg/mL of MEPT for 24 h were analyzed using an MTT assay (a). MEPT caused a change in cell morphology consistent with autophagy in HSC-4 cells (original magnification, ×200). Cells were treated with (A) 0 μg/mL, (B) 25 μg/mL, (C) 50 μg/mL, or (D) 100 μg/mL of MEPT for 24 h (b). Results are presented as the means ± standards deviation of three independent experiments. ∗∗∗P < 0.001 versus nontreated control.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4499625&req=5

fig1: MEPT-induced inhibition of proliferation and changes in cell morphology. HSC-4 cells treated with 0, 25, 50, 100, or 200 μg/mL of MEPT for 24 h were analyzed using an MTT assay (a). MEPT caused a change in cell morphology consistent with autophagy in HSC-4 cells (original magnification, ×200). Cells were treated with (A) 0 μg/mL, (B) 25 μg/mL, (C) 50 μg/mL, or (D) 100 μg/mL of MEPT for 24 h (b). Results are presented as the means ± standards deviation of three independent experiments. ∗∗∗P < 0.001 versus nontreated control.

Mentions: MEPT treatment for 24 hours restricted the proliferation rates of HSC-4 cells in a dose-dependent manner (Figure 1(a)) with inhibitory concentration (IC)50 values of 142.7 μg/mL at 24 h. After treatment, numerous HSC-4 cells had shrunk, become flattened, and developed intracytoplasmic vacuoles. In addition, a decrease in cell density was observed in the 50 and 100 μg/mL MEPT-treated groups (Figure 1(b)).


Autophagic Cell Death by Poncirus trifoliata Rafin., a Traditional Oriental Medicine, in Human Oral Cancer HSC-4 Cells.

Han HY, Park BS, Lee GS, Jeong SH, Kim H, Ryu MH - Evid Based Complement Alternat Med (2015)

MEPT-induced inhibition of proliferation and changes in cell morphology. HSC-4 cells treated with 0, 25, 50, 100, or 200 μg/mL of MEPT for 24 h were analyzed using an MTT assay (a). MEPT caused a change in cell morphology consistent with autophagy in HSC-4 cells (original magnification, ×200). Cells were treated with (A) 0 μg/mL, (B) 25 μg/mL, (C) 50 μg/mL, or (D) 100 μg/mL of MEPT for 24 h (b). Results are presented as the means ± standards deviation of three independent experiments. ∗∗∗P < 0.001 versus nontreated control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4499625&req=5

fig1: MEPT-induced inhibition of proliferation and changes in cell morphology. HSC-4 cells treated with 0, 25, 50, 100, or 200 μg/mL of MEPT for 24 h were analyzed using an MTT assay (a). MEPT caused a change in cell morphology consistent with autophagy in HSC-4 cells (original magnification, ×200). Cells were treated with (A) 0 μg/mL, (B) 25 μg/mL, (C) 50 μg/mL, or (D) 100 μg/mL of MEPT for 24 h (b). Results are presented as the means ± standards deviation of three independent experiments. ∗∗∗P < 0.001 versus nontreated control.
Mentions: MEPT treatment for 24 hours restricted the proliferation rates of HSC-4 cells in a dose-dependent manner (Figure 1(a)) with inhibitory concentration (IC)50 values of 142.7 μg/mL at 24 h. After treatment, numerous HSC-4 cells had shrunk, become flattened, and developed intracytoplasmic vacuoles. In addition, a decrease in cell density was observed in the 50 and 100 μg/mL MEPT-treated groups (Figure 1(b)).

Bottom Line: The methanol extract of P. trifoliata (MEPT) significantly decreased the proliferation of HSC-4 cells (inhibitory concentration (IC)50 = 142.7 μg/mL) in a dose-dependent manner.While there were no significant changes observed upon cell cycle analysis and ANNEXIN V and 7-AAD double staining in the MEPT-treated groups, the intensity of acidic vesicular organelle (AVO) staining and microtubule-associated protein 1 light chain (LC) 3-II protein expression increased in response to MEPT treatment.Taken together, our results indicate that MEPT is a potent autophagy agonist in oral cancer cells with antitumor therapeutic potential that acts through the mitogen-activated protein kinase (MAPK) pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Pathology, School of Dentistry, Institute of Translational Dental Sciences, Pusan National University, Yangsan, Republic of Korea.

ABSTRACT
Poncirus trifoliata Rafin. has long been used as anti-inflammatory and antiallergic agent to treat gastrointestinal disorders and pulmonary diseases such as indigestion, constipation, chest fullness, chest pain, bronchitis, and sputum in Korea. P. trifoliata extract has recently been reported to possess anticancer properties; however, its mechanisms of action remain unclear. In this study, its antiproliferative effects and possible mechanisms were investigated in HSC-4 cells. The methanol extract of P. trifoliata (MEPT) significantly decreased the proliferation of HSC-4 cells (inhibitory concentration (IC)50 = 142.7 μg/mL) in a dose-dependent manner. While there were no significant changes observed upon cell cycle analysis and ANNEXIN V and 7-AAD double staining in the MEPT-treated groups, the intensity of acidic vesicular organelle (AVO) staining and microtubule-associated protein 1 light chain (LC) 3-II protein expression increased in response to MEPT treatment. Furthermore, 3-methyladenine (3-MA, autophagy inhibitor) effectively blocked the MEPT-induced cytotoxicity of HSC-4 cells and triggered the activation of p38 and extracellular signal-regulated kinases (ERK) proteins. Taken together, our results indicate that MEPT is a potent autophagy agonist in oral cancer cells with antitumor therapeutic potential that acts through the mitogen-activated protein kinase (MAPK) pathway.

No MeSH data available.


Related in: MedlinePlus