Tae-Wook Chung1, Hyunju Choi2, Ji-Min Lee3, Sun-Hyung Ha4, Choong-Hwan Kwak5, Fukushi Abekura6, Jun-Young Park7, Young-Chae Chang8, Ki-Tae Ha9, Seung-Hak Cho10, Hyeun Wook Chang11, Young-Choon Lee12, Cheorl-Ho Kim13. 1. Division of Applied Medicine, School of Korean Medicine and Research Center for Healthy Aging, Pusan National University, Yangsan City, Gyeongsangnam-Do, Korea. Electronic address: chungtw@hanmail.net. 2. Department of Biological Sciences, SungKyunKwan University, Seoburo 2066, Jangan-Gu, Suwon, Gyunggi-Do 16419, Korea. Electronic address: chj204@skku.edu. 3. Department of Biological Sciences, SungKyunKwan University, Seoburo 2066, Jangan-Gu, Suwon, Gyunggi-Do 16419, Korea. Electronic address: jml@skku.edu. 4. Department of Biological Sciences, SungKyunKwan University, Seoburo 2066, Jangan-Gu, Suwon, Gyunggi-Do 16419, Korea. Electronic address: sunghyungha@skku.edu. 5. Department of Biological Sciences, SungKyunKwan University, Seoburo 2066, Jangan-Gu, Suwon, Gyunggi-Do 16419, Korea. Electronic address: kwak@skku.edu. 6. Department of Biological Sciences, SungKyunKwan University, Seoburo 2066, Jangan-Gu, Suwon, Gyunggi-Do 16419, Korea. Electronic address: pokusa6@hotmail.com. 7. Department of Biological Sciences, SungKyunKwan University, Seoburo 2066, Jangan-Gu, Suwon, Gyunggi-Do 16419, Korea. Electronic address: wnsdud2057@naver.com. 8. Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea. Electronic address: ycchang@cu.ac.kr. 9. Division of Applied Medicine, School of Korean Medicine and Research Center for Healthy Aging, Pusan National University, Yangsan City, Gyeongsangnam-Do, Korea. Electronic address: haggis@pnu.ac.kr. 10. Division of Enteric Diseases, Center for Infectious Diseases Research, Korea National Institute of Health, Heungdeok-gu, Cheongju 363-951, Korea. Electronic address: skcho38@hotmail.com. 11. College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea. Electronic address: hwchang@yu.ac.kr. 12. Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Korea. Electronic address: yclee@dau.ac.kr. 13. Division of Applied Medicine, School of Korean Medicine and Research Center for Healthy Aging, Pusan National University, Yangsan City, Gyeongsangnam-Do, Korea. Electronic address: chkimbio@skku.edu.
Abstract
ETHNOPHARMACOLOGY RELEVANCE: Oldenlandia diffusa (OD) has long been known as an apoptotic inducer in breast tumors in ethnomedicine. AIM OF THE STUDY: To scientifically confirm the anti-breast cancer effects of water, methanol (MeOH) and butanol (BuOH) extracts of O. diffusa on cell apoptosis, matrix metalloproteinases (MMPs), intercellular adhesion molecule (ICAM)-1 and intracellular signaling in MCF-7 breast cancer cells. MATERIALS AND METHODS: MeOH extracts (MOD) and BuOH extracts (BOD) were prepared and examined for their ability to inhibit phorbol myristate acetate (PMA)-induced matrix metalloproteinase (MMP)-9 and intercellular adhesion molecule (ICAM)-1 expressions in MCF-7 human breast cancer cells. Additionally, transwell migration, invasion and transcriptional activity were assessed. Results of immunofluorescence confocal microscopy for translocation of NF-κB and p-ERK and p-p38 were also checked. Finally, apoptotic signals including processed caspase-8, caspase-7, poly ADP-ribose polymerase, Bax and Bcl-2 were examined. RESULTS: MOD and BOD specifically inhibited PMA-induced MMP-9 expression as well as invasive and migration potential via ICAM-1. The inhibitory activity was also based on the suppressed transcriptional activity in MCF-7 breast cancer cells. Results of immunofluorescence confocal microscopy showed that translocation of NF-κB decreased upon BOD and MOD treatments, with a decreased level of p-ERK and p-p38 phosphorylation. In addition, treatment of MCF-7 cells with MOD and BOD activated apoptosis-linked proteins including enzymatically active forms of processed caspase-8, caspase-7 and poly ADP-ribose polymerase, together with increased expression of mitochondrial apoptotic protein, Bax and decreased expression of Bcl-2. CONCLUSION: The results indicate that OD as an anti-metastatic agent suppresses the metastatic response by targeting p-ERK, p-38 and NF-κB, thus reducing the invasion capacity of MCF-7 breast cancer cells through inhibition of MMP-9 and ICAM-1 expression and plays an important role in the regulation of breast cancer cell apoptosis.
ETHNOPHARMACOLOGY RELEVANCE: Oldenlandia diffusa (OD) has long been known as an apoptotic inducer in breast tumors in ethnomedicine. AIM OF THE STUDY: To scientifically confirm the anti-breast cancer effects of water, methanol (MeOH) and butanol (BuOH) extracts of O. diffusa on cell apoptosis, matrix metalloproteinases (MMPs), intercellular adhesion molecule (ICAM)-1 and intracellular signaling in MCF-7 breast cancer cells. MATERIALS AND METHODS: MeOH extracts (MOD) and BuOH extracts (BOD) were prepared and examined for their ability to inhibit phorbol myristate acetate (PMA)-induced matrix metalloproteinase (MMP)-9 and intercellular adhesion molecule (ICAM)-1 expressions in MCF-7 human breast cancer cells. Additionally, transwell migration, invasion and transcriptional activity were assessed. Results of immunofluorescence confocal microscopy for translocation of NF-κB and p-ERK and p-p38 were also checked. Finally, apoptotic signals including processed caspase-8, caspase-7, poly ADP-ribose polymerase, Bax and Bcl-2 were examined. RESULTS: MOD and BOD specifically inhibited PMA-induced MMP-9 expression as well as invasive and migration potential via ICAM-1. The inhibitory activity was also based on the suppressed transcriptional activity in MCF-7 breast cancer cells. Results of immunofluorescence confocal microscopy showed that translocation of NF-κB decreased upon BOD and MOD treatments, with a decreased level of p-ERK and p-p38 phosphorylation. In addition, treatment of MCF-7 cells with MOD and BOD activated apoptosis-linked proteins including enzymatically active forms of processed caspase-8, caspase-7 and poly ADP-ribose polymerase, together with increased expression of mitochondrial apoptotic protein, Bax and decreased expression of Bcl-2. CONCLUSION: The results indicate that OD as an anti-metastatic agent suppresses the metastatic response by targeting p-ERK, p-38 and NF-κB, thus reducing the invasion capacity of MCF-7 breast cancer cells through inhibition of MMP-9 and ICAM-1 expression and plays an important role in the regulation of breast cancer cell apoptosis.
Authors: Muhammad Khairi Ahmad; Nur Ainina Abdollah; Nurul Husna Shafie; Narazah Mohd Yusof; Siti Razila Abdul Razak Journal: Cancer Biol Med Date: 2018-02 Impact factor: 4.248