Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication
Current standard chemotherapy for late stage ovarian cancer is found unsuccessful due to relapse after completing the regimens. After completing platinum-based chemotherapy, 70% of patients develop relapse and resistance. Recent evidence proves ovarian cancer stem cells as the source of resistance....
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2017-04-01
|
| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317691689 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849428420891508736 |
|---|---|
| author | Yu-kai Su Wen-Chien Huang Wei-Hwa Lee Oluwaseun Adebayo Bamodu Muhammad Ary Zucha Indwiani Astuti Heri Suwito Chi-Tai Yeh Chien-Min Lin |
| author_facet | Yu-kai Su Wen-Chien Huang Wei-Hwa Lee Oluwaseun Adebayo Bamodu Muhammad Ary Zucha Indwiani Astuti Heri Suwito Chi-Tai Yeh Chien-Min Lin |
| author_sort | Yu-kai Su |
| collection | DOAJ |
| description | Current standard chemotherapy for late stage ovarian cancer is found unsuccessful due to relapse after completing the regimens. After completing platinum-based chemotherapy, 70% of patients develop relapse and resistance. Recent evidence proves ovarian cancer stem cells as the source of resistance. Therefore, treatment strategy to target both cancer stem cells and normal stem cells is essential. In this study, we developed a novel chalcone derivative as novel drug candidate for ovarian cancer treatment. We found that methoxyphenyl chalcone was effective to eliminate ovarian cancer cells when given either as monotherapy or in combination with cisplatin. We found that cell viability of ovarian cancer cells was decreased through apoptosis induction. Dephosphorylation of Bcl2-associated agonist of cell death protein was increased after methoxyphenyl chalcone treatment that led to activation of caspases. Interestingly, this drug also worked as a G2/M checkpoint modulator with alternative ways of DNA damage signal–evoking potential that might work to increase response after cisplatin treatment. In addition, methoxyphenyl chalcone was able to suppress autophagic flux and stemness regulator in ovarian spheroids that decreased their survival. Therefore, combination of methoxyphenyl chalcone and cisplatin showed synergistic effects. Taken together, we believe that our novel compound is a promising novel therapeutic agent for effective clinical treatment of ovarian cancer. |
| format | Article |
| id | doaj-art-2b5432e57c9c414fb7482f86f02da7c9 |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-2b5432e57c9c414fb7482f86f02da7c92025-08-20T03:28:43ZengSAGE PublishingTumor Biology1423-03802017-04-013910.1177/1010428317691689Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradicationYu-kai Su0Wen-Chien Huang1Wei-Hwa Lee2Oluwaseun Adebayo Bamodu3Muhammad Ary Zucha4Indwiani Astuti5Heri Suwito6Chi-Tai Yeh7Chien-Min Lin8Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, TaiwanMackay Junior College of Medicine, Nursing, and Management, Taipei, TaiwanDepartment of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, TaiwanDepartment of Medical Research and Education, Shuang Ho Hospital, Taipei Medical University, Taipei, TaiwanDepartment of Medical Research and Education, Shuang Ho Hospital, Taipei Medical University, Taipei, TaiwanDepartment of Chemistry, Faculty of Science and Technology, Airlangga University, Surabaya, IndonesiaDepartment of Pharmacology and Clinical Pharmacy, Universitas Gadjah Mada, Yogyakarta, IndonesiaDepartment of Medical Research and Education, Shuang Ho Hospital, Taipei Medical University, Taipei, TaiwanDivision of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, TaiwanCurrent standard chemotherapy for late stage ovarian cancer is found unsuccessful due to relapse after completing the regimens. After completing platinum-based chemotherapy, 70% of patients develop relapse and resistance. Recent evidence proves ovarian cancer stem cells as the source of resistance. Therefore, treatment strategy to target both cancer stem cells and normal stem cells is essential. In this study, we developed a novel chalcone derivative as novel drug candidate for ovarian cancer treatment. We found that methoxyphenyl chalcone was effective to eliminate ovarian cancer cells when given either as monotherapy or in combination with cisplatin. We found that cell viability of ovarian cancer cells was decreased through apoptosis induction. Dephosphorylation of Bcl2-associated agonist of cell death protein was increased after methoxyphenyl chalcone treatment that led to activation of caspases. Interestingly, this drug also worked as a G2/M checkpoint modulator with alternative ways of DNA damage signal–evoking potential that might work to increase response after cisplatin treatment. In addition, methoxyphenyl chalcone was able to suppress autophagic flux and stemness regulator in ovarian spheroids that decreased their survival. Therefore, combination of methoxyphenyl chalcone and cisplatin showed synergistic effects. Taken together, we believe that our novel compound is a promising novel therapeutic agent for effective clinical treatment of ovarian cancer.https://doi.org/10.1177/1010428317691689 |
| spellingShingle | Yu-kai Su Wen-Chien Huang Wei-Hwa Lee Oluwaseun Adebayo Bamodu Muhammad Ary Zucha Indwiani Astuti Heri Suwito Chi-Tai Yeh Chien-Min Lin Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication Tumor Biology |
| title | Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication |
| title_full | Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication |
| title_fullStr | Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication |
| title_full_unstemmed | Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication |
| title_short | Methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication |
| title_sort | methoxyphenyl chalcone sensitizes aggressive epithelial cancer to cisplatin through apoptosis induction and cancer stem cell eradication |
| url | https://doi.org/10.1177/1010428317691689 |
| work_keys_str_mv | AT yukaisu methoxyphenylchalconesensitizesaggressiveepithelialcancertocisplatinthroughapoptosisinductionandcancerstemcelleradication AT wenchienhuang methoxyphenylchalconesensitizesaggressiveepithelialcancertocisplatinthroughapoptosisinductionandcancerstemcelleradication AT weihwalee methoxyphenylchalconesensitizesaggressiveepithelialcancertocisplatinthroughapoptosisinductionandcancerstemcelleradication AT oluwaseunadebayobamodu methoxyphenylchalconesensitizesaggressiveepithelialcancertocisplatinthroughapoptosisinductionandcancerstemcelleradication AT muhammadaryzucha methoxyphenylchalconesensitizesaggressiveepithelialcancertocisplatinthroughapoptosisinductionandcancerstemcelleradication AT indwianiastuti methoxyphenylchalconesensitizesaggressiveepithelialcancertocisplatinthroughapoptosisinductionandcancerstemcelleradication AT herisuwito methoxyphenylchalconesensitizesaggressiveepithelialcancertocisplatinthroughapoptosisinductionandcancerstemcelleradication AT chitaiyeh methoxyphenylchalconesensitizesaggressiveepithelialcancertocisplatinthroughapoptosisinductionandcancerstemcelleradication AT chienminlin methoxyphenylchalconesensitizesaggressiveepithelialcancertocisplatinthroughapoptosisinductionandcancerstemcelleradication |