Limits...
The apoptotic mechanisms of MT-6, a mitotic arrest inducer, in human ovarian cancer cells

View Article: PubMed Central - PubMed

ABSTRACT

Patients with ovarian cancer are typically diagnosed at an advanced stage, resulting in poor prognosis since there are currently no effective early-detection screening tests for women at average-risk for ovarian cancer. Here, we investigated the effects of MT-6, a derivative of moscatilin, in ovarian cancer cells. Our investigation showed that MT-6 inhibited the proliferation and viability of ovarian cancer cells with submicromolar IC50 values. MT-6–treated SKOV3 cells showed significant cell cycle arrest at G2/M phase, followed by an increase in the proportion of cells in a sub-G1 phase. In addition, MT-6 induced a concentration-dependent increase in mitotic markers, mitotic kinases, cell cycle regulators of G2/M transition, and apoptosis-related markers in ovarian cancer cells. MT-6 treatment also induced mitochondrial membrane potential loss, JNK activation, and DR5 expression. Cotreatment of cells with the JNK inhibitor SP600125 considerably attenuated MT-6–induced apoptosis, mitochondria membrane potential loss, DR5 upregulation, and suppression of cell viability. MT-6 also inhibited tumor growth in an SKOV3 xenograft model without significant body weight loss. Together, our findings suggest that MT-6 is a potent anticancer agent with tumor-suppressive activity in vitro and in vivo that could be further investigated for ovarian cancer therapy in the future.

No MeSH data available.


Related in: MedlinePlus

Effects of MT-6 on cell cycle distribution in ovarian cancer cells.SKOV3 (A,B) or OVCAR3 (D,E) cells were treated with different concentrations (0.01–0.3 μM) of MT-6. After incubation for 24 h (A and D) or 48 h (B and E), the cell cycle was analyzed by flow cytometry after propidium iodide staining. Quantitative data (C and F) are based on flow cytometry histograms, and are presented as means ± S.E.M. of at least three independent experiments that yielded similar results (*P < 0.05 and **P < 0.01 compared with non-treated cells).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5384015&req=5

f2: Effects of MT-6 on cell cycle distribution in ovarian cancer cells.SKOV3 (A,B) or OVCAR3 (D,E) cells were treated with different concentrations (0.01–0.3 μM) of MT-6. After incubation for 24 h (A and D) or 48 h (B and E), the cell cycle was analyzed by flow cytometry after propidium iodide staining. Quantitative data (C and F) are based on flow cytometry histograms, and are presented as means ± S.E.M. of at least three independent experiments that yielded similar results (*P < 0.05 and **P < 0.01 compared with non-treated cells).

Mentions: To investigate the underlying mechanism of MT-6–induced cell-growth repression, we examined the effects of MT-6 on cell-cycle progression using flow cytometry. Treatment of SKOV3 cells with MT-6 for 24 h induced a significant concentration-dependent accumulation of cells in G2/M phase (Fig. 2A), whereas treatment for 48 h caused a clear increase in a subG1 cell population (Fig. 2B). As shown in Fig. 2C, cells began to accumulate in G2/M within 3 h of initiating treatment (lane 2), with a maximum occurring after 18 h treatment (lane 5); thereafter (18–24 h), subG1 phase cells started to accumulate (lane 5 to lane 10). Similar effects were also observed in OVCAR3 cells (Fig. 2D–F). Together, our data suggest that MT-6 induces G2/M-phase arrest and apoptosis in ovarian cancer cells. Our results showed that SKOV3 cells were more sensitive to MT-6 than OVCAR3 cells, and were therefore chosen for all subsequent experiments.


The apoptotic mechanisms of MT-6, a mitotic arrest inducer, in human ovarian cancer cells
Effects of MT-6 on cell cycle distribution in ovarian cancer cells.SKOV3 (A,B) or OVCAR3 (D,E) cells were treated with different concentrations (0.01–0.3 μM) of MT-6. After incubation for 24 h (A and D) or 48 h (B and E), the cell cycle was analyzed by flow cytometry after propidium iodide staining. Quantitative data (C and F) are based on flow cytometry histograms, and are presented as means ± S.E.M. of at least three independent experiments that yielded similar results (*P < 0.05 and **P < 0.01 compared with non-treated cells).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384015&req=5

f2: Effects of MT-6 on cell cycle distribution in ovarian cancer cells.SKOV3 (A,B) or OVCAR3 (D,E) cells were treated with different concentrations (0.01–0.3 μM) of MT-6. After incubation for 24 h (A and D) or 48 h (B and E), the cell cycle was analyzed by flow cytometry after propidium iodide staining. Quantitative data (C and F) are based on flow cytometry histograms, and are presented as means ± S.E.M. of at least three independent experiments that yielded similar results (*P < 0.05 and **P < 0.01 compared with non-treated cells).
Mentions: To investigate the underlying mechanism of MT-6–induced cell-growth repression, we examined the effects of MT-6 on cell-cycle progression using flow cytometry. Treatment of SKOV3 cells with MT-6 for 24 h induced a significant concentration-dependent accumulation of cells in G2/M phase (Fig. 2A), whereas treatment for 48 h caused a clear increase in a subG1 cell population (Fig. 2B). As shown in Fig. 2C, cells began to accumulate in G2/M within 3 h of initiating treatment (lane 2), with a maximum occurring after 18 h treatment (lane 5); thereafter (18–24 h), subG1 phase cells started to accumulate (lane 5 to lane 10). Similar effects were also observed in OVCAR3 cells (Fig. 2D–F). Together, our data suggest that MT-6 induces G2/M-phase arrest and apoptosis in ovarian cancer cells. Our results showed that SKOV3 cells were more sensitive to MT-6 than OVCAR3 cells, and were therefore chosen for all subsequent experiments.

View Article: PubMed Central - PubMed

ABSTRACT

Patients with ovarian cancer are typically diagnosed at an advanced stage, resulting in poor prognosis since there are currently no effective early-detection screening tests for women at average-risk for ovarian cancer. Here, we investigated the effects of MT-6, a derivative of moscatilin, in ovarian cancer cells. Our investigation showed that MT-6 inhibited the proliferation and viability of ovarian cancer cells with submicromolar IC50 values. MT-6&ndash;treated SKOV3 cells showed significant cell cycle arrest at G2/M phase, followed by an increase in the proportion of cells in a sub-G1 phase. In addition, MT-6 induced a concentration-dependent increase in mitotic markers, mitotic kinases, cell cycle regulators of G2/M transition, and apoptosis-related markers in ovarian cancer cells. MT-6 treatment also induced mitochondrial membrane potential loss, JNK activation, and DR5 expression. Cotreatment of cells with the JNK inhibitor SP600125 considerably attenuated MT-6&ndash;induced apoptosis, mitochondria membrane potential loss, DR5 upregulation, and suppression of cell viability. MT-6 also inhibited tumor growth in an SKOV3 xenograft model without significant body weight loss. Together, our findings suggest that MT-6 is a potent anticancer agent with tumor-suppressive activity in vitro and in vivo that could be further investigated for ovarian cancer therapy in the future.

No MeSH data available.


Related in: MedlinePlus