Limits...
The enriched fraction of Elephantopus scaber Triggers apoptosis and inhibits multi-drug resistance transporters in human epithelial cancer cells.

Beeran AA, Maliyakkal N, Rao CM, Udupa N - Pharmacogn Mag (2015 Apr-Jun)

Bottom Line: Medicinal plants have played an important role in the development of clinically useful anticancer agents.Cell cycle analysis and micronuclei assay were used to assess cell cycle specific pharmacological effects and drug induced genotoxicty.Thus, ES appears to be potential anticancer agent.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.

ABSTRACT

Background: Medicinal plants have played an important role in the development of clinically useful anticancer agents. Elephantopus scaber (Asteraceae) (ES) is widely used in Indian traditional system of medicine for the treatment of various ailments including cancer.

Objective: To investigate anticancer effects of ES in human epithelial cancer cells.

Materials and methods: Cytotoxicity of ethanolic extract of ES (ES-ET) and its fractions, such as ES Petroleum ether fraction (ES-PET), ES Dichloromethane fraction (ES DCM), n Butyl alcohol fraction (ES-BT), and ES-Rest (ES-R) were assessed in human epithelial cancer cell lines using sulforhodamine B (SRB) assay. Acridine orange/ethidium bromide assay and Hoechst 33342 assays were used to gauge induction of apoptosis. Cell cycle analysis and micronuclei assay were used to assess cell cycle specific pharmacological effects and drug induced genotoxicty. Further, the ability of ES to inhibit multi drug resistant (MDR) transporters (ABC-B1 and ABC-G2) was determined by Rhodamine (Rho) and Mitoxantrone (MXR) efflux assays.

Results: The enriched fraction of ES (ES DCM) possessed dose-dependent potent cytotoxicity in human epithelial cancer cells. Further, treatment of cancer cells (HeLa, A549, MCF-7, and Caco-2) with ES DCM showed hall mark properties of apoptosis (membrane blebbing, nuclear condensation etc.). Similarly, ES DCM caused enhanced sub G0 content and micronuclei formation indicating the induction of apoptosis and drug induced genotoxicity in cancer cells, respectively. Interestingly, ES DCM inhibited MDR transporters (ABC B1 and ABC G2) in cancer cells.

Conclusion: The enriched fraction of ES imparted cytotoxic effects, triggered apoptosis, induced genotoxicity, and inhibited MDR transporters in human epithelial cancer cells. Thus, ES appears to be potential anticancer agent.

No MeSH data available.


Related in: MedlinePlus

Dose-dependent cytotoxic effects of fractions of Elephantopus scaber (ES) in human epithelial cancer cells. Cervical carcinoma (HeLa), lung adenocarcinoma (A549), breast cancer cells (MCF-7, BT-474 and MDA-MB-231), and colon carcinoma (Caco2) cells were treated with ES Ethanolic extract (ES-ET); ES Petroleum ether fraction (ES-PET), ES Dichloromethane fraction (ES-DCM), ES n-butyl alcohol fraction and ES Rest fraction for 48 h. At the end of the treatment, percentage cell viability was determined by sulforhodamine B assay. Each point represents the mean ± standard error of the mean of three independent experiments performed in triplicates
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4378122&req=5

Figure 2: Dose-dependent cytotoxic effects of fractions of Elephantopus scaber (ES) in human epithelial cancer cells. Cervical carcinoma (HeLa), lung adenocarcinoma (A549), breast cancer cells (MCF-7, BT-474 and MDA-MB-231), and colon carcinoma (Caco2) cells were treated with ES Ethanolic extract (ES-ET); ES Petroleum ether fraction (ES-PET), ES Dichloromethane fraction (ES-DCM), ES n-butyl alcohol fraction and ES Rest fraction for 48 h. At the end of the treatment, percentage cell viability was determined by sulforhodamine B assay. Each point represents the mean ± standard error of the mean of three independent experiments performed in triplicates

Mentions: Cytotoxic effects of ES-ET, ES-PET, ES-DCM, ES-BT, and ES-R were evaluated on cervical (HeLa), lung (A549) breast (MCF-7, BT-474, MDA-231), and colon (Caco-2) cancer cells using SRB assay. Doxorubicin (positive control), caused a significant cytotoxic effects in the cancer cells with an IC50 values of 0.72 ± 0.02 μg/mL, 0.89 ± 0.03 μg/mL, 0.50 ± 0.04 μg/mL, 0.55 ± 0.03 μg/mL, 0.41 ± 0.02 μg/mL, and 0.75 ± 0.03 μg/mL against HeLa, A549, MCF-7, BT-474, MDA-MB-231, and Caco-2, respectively [Figure 1 and Table 1]. Similar to doxorubicin, the enriched fraction of ES (ES-DCM) possessed significant cytotoxic effects with dose-dependent reduction in the cell viability [Figure 1]. The IC50 values for ES-DCM in HeLa, A549, MCF-7, BT-474, MDA-MB-231, and Caco-2 were found to be 18.01 ± 0.73 μg/mL, 45.08 ± 1.99 μg/mL, 18.33 ± 1.18 μg/mL, 32.76 ± 0.69 μg/mL, 36.69 ± 1.24 μg/mL, and 40.28 ± 1.15 μg/mL, respectively [Table 1]. ES-ET also possessed dose-dependent cytotoxic effects in the cancer cells [Figure 1]. However, ES-PET, ES-BT, and ES-R did not show any significant cytotoxic effects in the cancer cells (IC50 > 100 μg/ml) [Figure 1 and Table 1]. Thus, these data revealed that the enriched fraction of ES (ES-DCM), but not other fractions (ES-PET, ES-BT, and ES-R), show dose-dependent cytotoxic effects against human epithelial cancer cells. Hence, further studies unraveling the anti-cancer mechanism were undertaken with the most-active enriched fraction of ES (ES-DCM).


The enriched fraction of Elephantopus scaber Triggers apoptosis and inhibits multi-drug resistance transporters in human epithelial cancer cells.

Beeran AA, Maliyakkal N, Rao CM, Udupa N - Pharmacogn Mag (2015 Apr-Jun)

Dose-dependent cytotoxic effects of fractions of Elephantopus scaber (ES) in human epithelial cancer cells. Cervical carcinoma (HeLa), lung adenocarcinoma (A549), breast cancer cells (MCF-7, BT-474 and MDA-MB-231), and colon carcinoma (Caco2) cells were treated with ES Ethanolic extract (ES-ET); ES Petroleum ether fraction (ES-PET), ES Dichloromethane fraction (ES-DCM), ES n-butyl alcohol fraction and ES Rest fraction for 48 h. At the end of the treatment, percentage cell viability was determined by sulforhodamine B assay. Each point represents the mean ± standard error of the mean of three independent experiments performed in triplicates
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4378122&req=5

Figure 2: Dose-dependent cytotoxic effects of fractions of Elephantopus scaber (ES) in human epithelial cancer cells. Cervical carcinoma (HeLa), lung adenocarcinoma (A549), breast cancer cells (MCF-7, BT-474 and MDA-MB-231), and colon carcinoma (Caco2) cells were treated with ES Ethanolic extract (ES-ET); ES Petroleum ether fraction (ES-PET), ES Dichloromethane fraction (ES-DCM), ES n-butyl alcohol fraction and ES Rest fraction for 48 h. At the end of the treatment, percentage cell viability was determined by sulforhodamine B assay. Each point represents the mean ± standard error of the mean of three independent experiments performed in triplicates
Mentions: Cytotoxic effects of ES-ET, ES-PET, ES-DCM, ES-BT, and ES-R were evaluated on cervical (HeLa), lung (A549) breast (MCF-7, BT-474, MDA-231), and colon (Caco-2) cancer cells using SRB assay. Doxorubicin (positive control), caused a significant cytotoxic effects in the cancer cells with an IC50 values of 0.72 ± 0.02 μg/mL, 0.89 ± 0.03 μg/mL, 0.50 ± 0.04 μg/mL, 0.55 ± 0.03 μg/mL, 0.41 ± 0.02 μg/mL, and 0.75 ± 0.03 μg/mL against HeLa, A549, MCF-7, BT-474, MDA-MB-231, and Caco-2, respectively [Figure 1 and Table 1]. Similar to doxorubicin, the enriched fraction of ES (ES-DCM) possessed significant cytotoxic effects with dose-dependent reduction in the cell viability [Figure 1]. The IC50 values for ES-DCM in HeLa, A549, MCF-7, BT-474, MDA-MB-231, and Caco-2 were found to be 18.01 ± 0.73 μg/mL, 45.08 ± 1.99 μg/mL, 18.33 ± 1.18 μg/mL, 32.76 ± 0.69 μg/mL, 36.69 ± 1.24 μg/mL, and 40.28 ± 1.15 μg/mL, respectively [Table 1]. ES-ET also possessed dose-dependent cytotoxic effects in the cancer cells [Figure 1]. However, ES-PET, ES-BT, and ES-R did not show any significant cytotoxic effects in the cancer cells (IC50 > 100 μg/ml) [Figure 1 and Table 1]. Thus, these data revealed that the enriched fraction of ES (ES-DCM), but not other fractions (ES-PET, ES-BT, and ES-R), show dose-dependent cytotoxic effects against human epithelial cancer cells. Hence, further studies unraveling the anti-cancer mechanism were undertaken with the most-active enriched fraction of ES (ES-DCM).

Bottom Line: Medicinal plants have played an important role in the development of clinically useful anticancer agents.Cell cycle analysis and micronuclei assay were used to assess cell cycle specific pharmacological effects and drug induced genotoxicty.Thus, ES appears to be potential anticancer agent.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.

ABSTRACT

Background: Medicinal plants have played an important role in the development of clinically useful anticancer agents. Elephantopus scaber (Asteraceae) (ES) is widely used in Indian traditional system of medicine for the treatment of various ailments including cancer.

Objective: To investigate anticancer effects of ES in human epithelial cancer cells.

Materials and methods: Cytotoxicity of ethanolic extract of ES (ES-ET) and its fractions, such as ES Petroleum ether fraction (ES-PET), ES Dichloromethane fraction (ES DCM), n Butyl alcohol fraction (ES-BT), and ES-Rest (ES-R) were assessed in human epithelial cancer cell lines using sulforhodamine B (SRB) assay. Acridine orange/ethidium bromide assay and Hoechst 33342 assays were used to gauge induction of apoptosis. Cell cycle analysis and micronuclei assay were used to assess cell cycle specific pharmacological effects and drug induced genotoxicty. Further, the ability of ES to inhibit multi drug resistant (MDR) transporters (ABC-B1 and ABC-G2) was determined by Rhodamine (Rho) and Mitoxantrone (MXR) efflux assays.

Results: The enriched fraction of ES (ES DCM) possessed dose-dependent potent cytotoxicity in human epithelial cancer cells. Further, treatment of cancer cells (HeLa, A549, MCF-7, and Caco-2) with ES DCM showed hall mark properties of apoptosis (membrane blebbing, nuclear condensation etc.). Similarly, ES DCM caused enhanced sub G0 content and micronuclei formation indicating the induction of apoptosis and drug induced genotoxicity in cancer cells, respectively. Interestingly, ES DCM inhibited MDR transporters (ABC B1 and ABC G2) in cancer cells.

Conclusion: The enriched fraction of ES imparted cytotoxic effects, triggered apoptosis, induced genotoxicity, and inhibited MDR transporters in human epithelial cancer cells. Thus, ES appears to be potential anticancer agent.

No MeSH data available.


Related in: MedlinePlus