Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis.
Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human M...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3934844?pdf=render |
| _version_ | 1818848138994122752 |
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| author | Xu Wang Jonathan J Beitler Hong Wang Michael J Lee Wen Huang Lydia Koenig Sreenivas Nannapaneni A R M Ruhul Amin Michael Bonner Hyung Ju C Shin Zhuo Georgia Chen Jack L Arbiser Dong M Shin |
| author_facet | Xu Wang Jonathan J Beitler Hong Wang Michael J Lee Wen Huang Lydia Koenig Sreenivas Nannapaneni A R M Ruhul Amin Michael Bonner Hyung Ju C Shin Zhuo Georgia Chen Jack L Arbiser Dong M Shin |
| author_sort | Xu Wang |
| collection | DOAJ |
| description | Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB-C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1 cells and the MDR derivatives (IC50 ranging 3.35 ± 0.13 µg/ml to 2.77 ± 0.22 µg/ml), despite their significant differences in response to paclitaxel (IC50 ranging 1.66 ± 0.09 ng/ml to 6560.9 ± 439.52 ng/ml). Honokiol induced mitochondria-dependent and death receptor-mediated apoptosis in MDR KB cells, which was associated with inhibition of EGFR-STAT3 signaling and downregulation of STAT3 target genes. Combined treatment with honokiol and paclitaxel synergistically augmented cytotoxicity in MDR KB cells, compared with treatment with either agent alone in vitro. Importantly, the combined treatment significantly inhibited in vivo growth of KB-8-5 tumors in a subcutaneous model. Tumor tissues from the combination group displayed a significant inhibition of Ki-67 expression and an increase in TUNEL-positive cells compared with the control group. These results suggest that targeting multidrug resistance using honokiol in combination with chemotherapy drugs may provide novel therapeutic opportunities. |
| first_indexed | 2024-12-19T06:12:35Z |
| format | Article |
| id | doaj.art-8adcbd5bb3db49ff978bdabbbdb1a175 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T06:12:35Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8adcbd5bb3db49ff978bdabbbdb1a1752022-12-21T20:32:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8636910.1371/journal.pone.0086369Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis.Xu WangJonathan J BeitlerHong WangMichael J LeeWen HuangLydia KoenigSreenivas NannapaneniA R M Ruhul AminMichael BonnerHyung Ju C ShinZhuo Georgia ChenJack L ArbiserDong M ShinResistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB-C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1 cells and the MDR derivatives (IC50 ranging 3.35 ± 0.13 µg/ml to 2.77 ± 0.22 µg/ml), despite their significant differences in response to paclitaxel (IC50 ranging 1.66 ± 0.09 ng/ml to 6560.9 ± 439.52 ng/ml). Honokiol induced mitochondria-dependent and death receptor-mediated apoptosis in MDR KB cells, which was associated with inhibition of EGFR-STAT3 signaling and downregulation of STAT3 target genes. Combined treatment with honokiol and paclitaxel synergistically augmented cytotoxicity in MDR KB cells, compared with treatment with either agent alone in vitro. Importantly, the combined treatment significantly inhibited in vivo growth of KB-8-5 tumors in a subcutaneous model. Tumor tissues from the combination group displayed a significant inhibition of Ki-67 expression and an increase in TUNEL-positive cells compared with the control group. These results suggest that targeting multidrug resistance using honokiol in combination with chemotherapy drugs may provide novel therapeutic opportunities.http://europepmc.org/articles/PMC3934844?pdf=render |
| spellingShingle | Xu Wang Jonathan J Beitler Hong Wang Michael J Lee Wen Huang Lydia Koenig Sreenivas Nannapaneni A R M Ruhul Amin Michael Bonner Hyung Ju C Shin Zhuo Georgia Chen Jack L Arbiser Dong M Shin Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis. PLoS ONE |
| title | Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis. |
| title_full | Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis. |
| title_fullStr | Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis. |
| title_full_unstemmed | Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis. |
| title_short | Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis. |
| title_sort | honokiol enhances paclitaxel efficacy in multi drug resistant human cancer model through the induction of apoptosis |
| url | http://europepmc.org/articles/PMC3934844?pdf=render |
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