Use of herbal medicines and natural products: An alternative approach to overcoming the apoptotic resistance of pancreatic cancer |
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| Affiliation: | 1. Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan;2. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;3. National Museum of Marine Biology & Aquarium, Pingtung 944, Taiwan;4. Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan;5. Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;6. Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan;7. Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan;8. Department of Biochemistry, University of Toronto, Toronto M5G2R3, Canada;9. Institute of Oceanography, National Taiwan University, Taipei 112, Taiwan;10. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan;11. Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan;12. Frontier Center for Ocean Science and Technology, National Sun Yat-sen University, Kaohsiung 804, Taiwan;1. Department of Thoracic Oncology, LungenClinic Grosshansdorf; member of the Airway research center north (ARCN) as part of the German Centre for Lung Research (DZL), Grosshansdorf, Germany;2. Division of Hematology/Oncology, UC Davis Comprehensive Cancer Center, Sacramento, USA;1. School of Traditional Chinese Medicine, Southern Medical University, 1063 Shatai Road, Guangzhou 510515, China;2. School of Pharmaceutical, Hunan University of Chinese Medicine, Xueshi Road, Changsha 410208, China;1. Center for Marine Natural Products and Drug Discovery, School of Earth and Environmental Sciences, Seoul National University, NS-80, Seoul 151-747, Republic of Korea;2. Department of Chemistry and Nano Science, Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea;3. Research Institute of Oceanography, Seoul National University, NS-80, Seoul 151-747, Republic of Korea;4. College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan 712-749, Republic of Korea;1. School of Chinese Medicine, China Medical University, Taichung, Taiwan;2. Divisions of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan;3. Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan;4. Asia University, Taichung, Taiwan;5. Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan;6. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;7. Rheumatism Research Center, China Medical University Hospital, Taichung, Taiwan;8. School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;9. Department of Cosmetic Science, Providence University, Taichung, Taiwan;1. Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People''s Republic of China;2. Department of Neurosurgery, The Affiliated Dushuhu Hospital of Soochow University, Suzhou, Jiangsu Province, People''s Republic of China;3. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province, People''s Republic of China |
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| Abstract: | Pancreatic cancer has a poor prognosis with a 5-year survival rate of <5%. It does not respond well to either chemotherapy or radiotherapy, due partly to apoptotic resistance (AR) of the cancer cells. AR has been attributed to certain genetic abnormalities or defects in apoptotic signaling pathways. In pancreatic cancer, significant mutations of K-ras and p53, constitutive activation of NFκB, over-expression of heat shock proteins (Hsp90, Hsp70), histone deacetylase (HDACs) and the activities of other proteins (COX-2, Nrf2 and bcl-2 family members) are closely linked with resistance to apoptosis and invasion. AR has also been associated with aberrant signaling of MAPK, PI3K–AKT, JAK/STAT, SHH, Notch, and Wnt/β-catenin pathways. Strategies targeting these signaling molecules and pathways provide an alternative for overcoming AR in pancreatic cancer. The use of herbal medicines or natural products (HM/NPs) alone or in combination with conventional anti-cancer agents has been shown to produce beneficial effects through actions upon multiple molecular pathways involved in AR. The current standard first-line chemotherapeutic agents for pancreatic cancer are gemcitabine (Gem) or Gem-containing combinations; however, the efficacy is dissatisfied and this limitation is largely attributed to AR. Meanwhile, emerging data have pointed to a combination of HM/NPs that may augment the sensitivity of pancreatic cancer cells to Gem. Greater understanding of how these compounds affect the molecular mechanisms of apoptosis may propel development of HM/NPs as anti-cancer agents and/or adjuvant therapies forward.In this review, we give a critical appraisal of the use of HM/NPs alone and in combination with anti-cancer drugs. We also discuss the potential regulatory mechanisms whereby AR is involved in these protective pathways. |
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| Keywords: | Bruceine D Chinese medicine Eriocalyxin B Gemcitabine Reactive oxygen species |
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