Brown algae as a source of bioactive compounds for pancreatic cancer treatment Thanh Trung Dang B.Eng (Nha Trang University, Khanh Hoa, Vietnam) MSc (Nha Trang University, Khanh Hoa, Vietnam) A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy in Food Science School of Environmental and Life Sciences, Faculty of Science University of Newcastle Australia May 2018 STATEMENT OF ORIGINALITY I hereby certify that to the best of my knowledge and belief this thesis is my own work and contains no material previously published or written by another person except where due references and acknowledgements are made. It contains no material which has been previously submitted by me for the award of any other degree or diploma in any university or other tertiary institution. Thanh Trung Dang Date: 6/5/2018 i DECLARATION OF AUTHORSHIP I hereby certify that this thesis is in the form of a series of 8 papers. I have included as part of the thesis a written statement from each co-author, endorsed in writing by the Faculty Assistant Dean (Research Training), attesting to my contribution to any jointly authored papers. Thanh Trung Dang Date: 6/5/2018 ii ACKNOWLEDGEMENTS Firstly, I would like to give a great appreciation to my supervisors: Principal supervisor: A/Prof. Christopher J. Scarlett; Co-supervisors: A/Prof. Michael C. Bowyer and Dr. Ian A. Van Altena for their supervision and support during my PhD course. The suggestions and encouragement from the supervisor panel played an important role in my research achievements. I acknowledge the financial support from University of Newcastle; the Vietnamese Government through the Ministry of Education and Training; the Ministry of Agriculture and Rural Development for awarding a VIED-TUIT scholarship, which enabled me to study for a PhD at the University of Newcastle, with full cover for academic expenses, as well as living and travellingallowances. I highly appreciated the contribution of brown algae as the material for my PhD project from Dr. Maria Schreider (School of Environmental and Life Sciences, Faculty of Science, University of Newcastle), in particular for identifying algal species and allowing her students assist in the collection of the samples. I would like to say thank you to Dr. Quan V. Vuong, Dr. Danielle Bond and other PhD students in Food Science, technical staff and administrative staff for helping me to overcome the difficulties in the laboratory and administrative works. Finally, I would like to say thank my colleagues and friends from Nha Trang University, Vietnam for their encouragement. A very special thank you is given to my family (parents, young brother), who have always been behind me, encouraging and inspiring me during my PhD project. iii LIST OF PUBLICATIONS INCLUDED AS PART OF THE THESIS I warrant that I have obtained, where necessary, permission from the copyright owners to use any third party copyright material reproduced in the thesis, or to use any of my own published work in which the copyright is held by another party. 1. Paper I: Dang TT, Bowyer MC, Van Altena IA & Scarlett CJ. (2018). Comparison of chemical profile and antioxidant properties of the brown algae, International Journal of Food Science & Technology 51(1): 174-181. doi: 10.1111/ijfs.13571. 2. Paper II: Dang TT, Vuong QV, Schreider MJ, Bowyer MC, Van Altena IA & Scarlett CJ. (2017). The Effects of Drying on Physico-Chemical Properties and Antioxidant Capacity of the Brown Alga (Hormosira banksii (Turner) Decaisne). Journal of Food Process and Preservation 41(4): e13025. doi.org/10.1111/jfpp.13025. 3. Paper III: Dang TT, Vuong QV, Schreider MJ, Bowyer MC, Van Altena IA & Scarlett CJ (2017). Optimisation of ultrasound-assisted extraction conditions for phenolic content and antioxidant activities of the alga Hormosira banksii using response surface methodology. Journal of Applied Phycology 29(6): 3161-3173. doi.org/10.1007/s10811-017-1162-y. 4. Paper IV: Dang TT, Bowyer MC, Van Altena IA & Scarlett CJ. (2017). Optimum conditions of microwave assisted extraction for phenolic compounds and antioxidant capacity of the brown alga Sargassum vestitum. Separation Science and Technology (In Press). doi.org/10.1080/01496395.2017.1414845. 5. Paper V: Dang TT, Vuong QV, Bowyer MC & Scarlett CJ. Chemical profile and antioxidant activities of the crude extract and different fractions prepared from the brown alga Hormosira banksii (Turner) Decaisne. Submitted to Journal of BotanicaMarina. 6. Paper VI: Dang TT, Bhuyan DJ, Bond DR, Bowyer MC, Van Altena IA & Scarlett CJ. iv Fucoxanthin content, isolation and cytotoxic activity against pancreatic cancer from brown alga Hormosira banksii (Turner) Decaisne. Submitted to Journal of Biotechnology. 7. Paper VII: Dang TT, Sakoff JA, Bowyer MC, Van Altena IA & Scarlett CJ. Antioxidant and cytotoxic activity (in vitro) of phlorotannin-enriched fractions from the brown alga Hormosira banksii (Turner) Decaisne. Submitted to Journal of Marine Biotechnology. 8. Paper VIII: Dang TT & Scarlett CJ. Extraction and cytotoxic activity of the sulfated polysaccharides (fucoidans) against pancreatic cancer in vitro from brown alga Hormosira banksii (Turner) Decaisne. Submitted to Journal of Biomedicineand Pharmacotherapy. v STATEMENT OF AUTHORS' CONTRIBUTION TO THE PAPERS To whom it may concern, We, Christopher J. Scarlett, Michael C. Bowyer and Ian A. Van Altena as co-authors with contribution of planning, giving the giving the suggestions and editing the paper, attest that research higher degree candidate, Thanh Trung Dang, was the principle contributor to the planning, execution, analyses of the experiments and the writing of the published research paper entitled “Comparison of chemical profile and antioxidant properties of the brown algae”, International Journal of Food Science & Technology 51(1): 174-181. doi:10.1111/ijfs.13571. Dr. Ian A. Van Altena Date: 27/4/2018 Thanh Trung Dang Date: 26/4/2018 I have seen this paper and I agree with the signatories above that it represents a substantial amount of research work and can be part of Thanh Trung Dang’ s PhD thesis. Professor Frances Martin Assistant Dean Research Training (ADRT) Date: vi STATEMENT OF AUTHORS' CONTRIBUTION TO THE PAPERS To whom it may concern, We, Quan V. Vuong, Maria J. Schreider, Christopher J. Scarlett, Michael C. Bowyer and Ian A. Van Altena as co-authors with contribution of planning, giving the suggestions and editing the paper, attest that research higher degree candidate, Thanh Trung Dang, was the principle contributor to the planning, execution, analyses of the experiments and the writing of the published research paper entitled “The Effects of Drying on Physico-Chemical Properties and Antioxidant Capacity of the Brown Alga (Hormosira banksii (Turner) Decaisne)”. Journal of Food Process and Preservation 41(4): e13025. doi.org/10.1111/jfpp.13025. Dr. Ian A. Van Altena Date: 27/4/2018 Thanh Trung Dang Date: 26/4/2018 I have seen this paper and I agree with the signatories above that it represents a substantial amount of research work and can be part of Thanh Trung Dang’ s PhD thesis. vii STATEMENT OF AUTHORS' CONTRIBUTION TO THE PAPERS To whom it may concern, We, Quan V. Vuong, Maria J. Schreider, Christopher J. Scarlett, Michael C. Bowyer and Ian A. Van Altena as co-authors with contribution of planning, giving the giving the suggestions and editing the paper, attest that research higher degree candidate, Thanh Trung Dang, was the principle contributor to the planning, execution, analyses of the experiments and the writing of the published research paper entitled “Optimisation of ultrasound-assisted extraction conditions for phenolic content and antioxidant activities of the alga Hormosira banksii using response surface methodology”. Journal of Applied Phycology 29(6): 3161-3173. doi.org/10.1007/s10811-017-1162-y. Dr. Ian A. Van Altena Date: 27/4/2018 Thanh Trung Dang Date: 26/4/2018 I have seen this paper and I agree with the signatories above that it represents a substantial amount of research work and can be part of Thanh Trung Dang’ s PhD thesis. Professor Frances Martin Assistant Dean Research Training (ADRT) Date: viii STATEMENT OF AUTHORS' CONTRIBUTION TO THE PAPERS To whom it may concern, We, Christopher J. Scarlett, Michael C. Bowyer and Ian A. Van Altena as co-authors with contribution of planning, giving the feedbacks and editing the paper, attest that research higher degree candidate, Thanh Trung Dang, was the principle contributor to the planning, execution, analyses of the experiments and the writing of the published research paper entitled “Optimum conditions of microwave assisted extraction for phenolic compounds and antioxidant capacity of the brown alga Sargassum vestitum” Separation Science and Technology (In Press). doi.org/10.1080/01496395.2017.1414845. Dr. Ian A. Van Altena Date: 27/4/2018 Thanh Trung Dang Date: 26/4/2018 I have seen this paper and I agree with the signatories above that it represents a substantial amount of research work and can be part of Thanh Trung Dang’ s PhD thesis. Professor Frances Martin Assistant Dean Research Training (ADRT) Date: ix STATEMENT OF AUTHORS' CONTRIBUTION TO THE PAPERS To whom it may concern, We, Quan V. Vuong, Christopher J. Scarlett, Michael C. Bowyer as co-authors with contribution of planning, giving the suggestions and editing the paper, attest that research higher degree candidate, Thanh Trung Dang, was the principle contributor to the planning, execution, analyses of the experiments and the writing of the published research paper entitled “Chemical profile and antioxidant activities of the crude extract and different fractions prepared from the brown alga Hormosira banksii (Turner) Decaisne”. Submitted to Journal of Botanica Marina. Thanh Trung Dang Date: 26/4/2018 I have seen this paper and I agree with the signatories above that it represents a substantial amount of research work and can be part of Thanh Trung Dang’ s PhD thesis.