3,3′-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen species
Context: A major problem in the treatment of cancer is the development of toxic side effects and resistance to chemotherapy. The use of plant compounds to overcome resistance and prevent toxicity is a potential strategy for treatment. Objective: We evaluated whether 3,3′-diindolylmethane (DIM) enhan...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/13880209.2018.1495747 |
| _version_ | 1819211473534058496 |
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| author | Susan Lanza-Jacoby Guanjun Cheng |
| author_facet | Susan Lanza-Jacoby Guanjun Cheng |
| author_sort | Susan Lanza-Jacoby |
| collection | DOAJ |
| description | Context: A major problem in the treatment of cancer is the development of toxic side effects and resistance to chemotherapy. The use of plant compounds to overcome resistance and prevent toxicity is a potential strategy for treatment. Objective: We evaluated whether 3,3′-diindolylmethane (DIM) enhanced the sensitivity of breast cancer cells to docetaxel (DOC). Materials and methods: MDA-MB231 and Sk-BR-3 cells were treated with and without 25 or 50 µM of DIM and 1 nM of DOC for 48 and 72 h, respectively. MTT assay was used to measure cell survival. Apoptosis and intracellular reactive oxygen species (ROS) were determined by flow cytometry. The expression of proteins regulating ROS production and apoptosis was evaluated by immunoblotting technique. Results: Combining 25 µM of DIM with 1 nM DOC decreased cell survival by 42% in MDA-MB231 cells and 59% in Sk-BR-3 cells compared to control, DIM, or DOC (p ≤ 0.05). The combination treatment increased apoptosis over 20% (p ≤ 0.01) in both cell lines, which was associated with decreased Bcl-2, increased Bax, cleaved PARP and activated JNK (p ≤ 0.01). ROS production increased by 46.5% in the MDA-MB231 and 29.3% in Sk-BR-3 cells with the combination compared to DIM or DOC alone. Pretreating cells with N-acetyl-cysteine or Tiron abrogated the anti-survival effect of the combination. The increase in ROS was associated with a 54% decrease in MnSOD and 47% increase in NOX2 protein compared to the other groups. Conclusions: Our findings indicated that DIM enhances the sensitivity of breast cancer cells to DOC treatment by increasing ROS, which led to decreased cell survival and apoptosis. |
| first_indexed | 2024-12-23T06:27:38Z |
| format | Article |
| id | doaj.art-63abb313b5e54aadbcb7e615033e1b9b |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-23T06:27:38Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-63abb313b5e54aadbcb7e615033e1b9b2022-12-21T17:57:00ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162018-01-0156140741410.1080/13880209.2018.149574714957473,3′-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen speciesSusan Lanza-Jacoby0Guanjun Cheng1Thomas Jefferson UniversityThomas Jefferson UniversityContext: A major problem in the treatment of cancer is the development of toxic side effects and resistance to chemotherapy. The use of plant compounds to overcome resistance and prevent toxicity is a potential strategy for treatment. Objective: We evaluated whether 3,3′-diindolylmethane (DIM) enhanced the sensitivity of breast cancer cells to docetaxel (DOC). Materials and methods: MDA-MB231 and Sk-BR-3 cells were treated with and without 25 or 50 µM of DIM and 1 nM of DOC for 48 and 72 h, respectively. MTT assay was used to measure cell survival. Apoptosis and intracellular reactive oxygen species (ROS) were determined by flow cytometry. The expression of proteins regulating ROS production and apoptosis was evaluated by immunoblotting technique. Results: Combining 25 µM of DIM with 1 nM DOC decreased cell survival by 42% in MDA-MB231 cells and 59% in Sk-BR-3 cells compared to control, DIM, or DOC (p ≤ 0.05). The combination treatment increased apoptosis over 20% (p ≤ 0.01) in both cell lines, which was associated with decreased Bcl-2, increased Bax, cleaved PARP and activated JNK (p ≤ 0.01). ROS production increased by 46.5% in the MDA-MB231 and 29.3% in Sk-BR-3 cells with the combination compared to DIM or DOC alone. Pretreating cells with N-acetyl-cysteine or Tiron abrogated the anti-survival effect of the combination. The increase in ROS was associated with a 54% decrease in MnSOD and 47% increase in NOX2 protein compared to the other groups. Conclusions: Our findings indicated that DIM enhances the sensitivity of breast cancer cells to DOC treatment by increasing ROS, which led to decreased cell survival and apoptosis.http://dx.doi.org/10.1080/13880209.2018.1495747chemoresistanceapoptosisoxidative stressplant compoundschemotherapy |
| spellingShingle | Susan Lanza-Jacoby Guanjun Cheng 3,3′-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen species Pharmaceutical Biology chemoresistance apoptosis oxidative stress plant compounds chemotherapy |
| title | 3,3′-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen species |
| title_full | 3,3′-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen species |
| title_fullStr | 3,3′-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen species |
| title_full_unstemmed | 3,3′-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen species |
| title_short | 3,3′-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen species |
| title_sort | 3 3 diindolylmethane enhances apoptosis in docetaxel treated breast cancer cells by generation of reactive oxygen species |
| topic | chemoresistance apoptosis oxidative stress plant compounds chemotherapy |
| url | http://dx.doi.org/10.1080/13880209.2018.1495747 |
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