File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

postgraduate thesis: Identification and characterization of bioactive compounds in Spatholobus suberectus targeting on LDH-A in breast cancer

TitleIdentification and characterization of bioactive compounds in Spatholobus suberectus targeting on LDH-A in breast cancer
Authors
Issue Date2012
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Wang, Z. [王志宇]. (2012). Identification and characterization of bioactive compounds in Spatholobus suberectus targeting on LDH-A in breast cancer. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4832942
AbstractAlthough clinical outcomes of some cancer have been greatly improved by advancements made in surgery, chemo or radiotherapy and development of novel strategies such as molecular targeted therapy, Traditional Chinese Medicine (TCM) is particularly appreciated for cancer therapy in China based on its 5,000-year-old history, well established theoretical system and numerous exciting case reports. However, due to lack of quality assurance, laboratory evidences and well-designed clinical trials, TCM always encounters much skepticism and pessimism by the West. The study aims to identify the bioactive compounds in a Chinese herb Spatholobus suberectus (SS, 雞血藤) by targeting on lactate dehydrogenase A (LDH-A) in breast cancer. Glycolysis inhibition has been considered as important strategy to block cancer energy metabolism and therefore suppressing cancer growth. LDH-A has been demonstrated to be up-regulated in various cancer cells. In our study, 46 breast cancer specimens were collected to study the relation between LDH-A expression and clinicopathological characteristics including menopause, tumor size, node involvement, differentiation and pathological subtypes classified by estrogen receptor (ER), progesterone receptor (PR) and Her-2. LDH-A expression was found to be correlated significantly with breast cancer size and independent with other clinicopathological factors. LDH-A silencing in breast cancer cell lines MDA-MB-231 and MCF-7 resulted in an inhibited breast cancer cell proliferation, elevated intracellular oxidative stress, induction of mitochondiral pathway apoptosis and limited tumorigenic ability, indicating that LDH-A inhibition might offer a promising therapeutic strategy for breast cancer. SS is historically recommended to invigorate blood circulation and has been prescribed to treat diseases relating to blood stasis syndromes including menstrual abnormalities, anemia, numbness of the limbs, arthritis and cancer, etc. Our following study revealed that SS aqueous extracts could significantly inhibited breast cancer LDH-A expression and activity in both in vitro and in vivo models built by MDA-MB-231 and MCF-7 cell lines. Bioactivity guided fractionation based on LDH-A activity, apoptosis and LDH-A expression further identified epigallocatechin (EGC) as the key compound responsible for the inhibited LDH-A expression. Mechanistic studies found that the inhibitory effect of EGC on LDH-A expression was mainly through promoting Hypoxia inducible factor-1α (HIF-1α) proteasome degradation rather than inhibiting transcription activity, which might be correlated with decreased binding between HIF-1α and Hsp90. Consistent with in vitro findings, EGC was also demonstrated effecitve in suppressing breast cancer growth in vivo correlating to down-regulation of LDH-A, HIF-1α and triggerment of apoptosis. This study provides preliminary laboratory evidences for applying SS in breast cancer therapy. However, further research is needed to evaluate its metabolism, the synergistic effects with chemotherapeutic agents and clinical efficiency.
DegreeDoctor of Philosophy
SubjectPlant bioactive compounds.
Spatholobus - Therapeutic use.
Lactate dehydrogenase.
Breast - Cancer - Treatment.
Dept/ProgramChinese Medicine
Persistent Identifierhttp://hdl.handle.net/10722/188741

 

DC FieldValueLanguage
dc.contributor.authorWang, Zhiyu-
dc.contributor.author王志宇-
dc.date.accessioned2013-09-08T15:07:50Z-
dc.date.available2013-09-08T15:07:50Z-
dc.date.issued2012-
dc.identifier.citationWang, Z. [王志宇]. (2012). Identification and characterization of bioactive compounds in Spatholobus suberectus targeting on LDH-A in breast cancer. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4832942-
dc.identifier.urihttp://hdl.handle.net/10722/188741-
dc.description.abstractAlthough clinical outcomes of some cancer have been greatly improved by advancements made in surgery, chemo or radiotherapy and development of novel strategies such as molecular targeted therapy, Traditional Chinese Medicine (TCM) is particularly appreciated for cancer therapy in China based on its 5,000-year-old history, well established theoretical system and numerous exciting case reports. However, due to lack of quality assurance, laboratory evidences and well-designed clinical trials, TCM always encounters much skepticism and pessimism by the West. The study aims to identify the bioactive compounds in a Chinese herb Spatholobus suberectus (SS, 雞血藤) by targeting on lactate dehydrogenase A (LDH-A) in breast cancer. Glycolysis inhibition has been considered as important strategy to block cancer energy metabolism and therefore suppressing cancer growth. LDH-A has been demonstrated to be up-regulated in various cancer cells. In our study, 46 breast cancer specimens were collected to study the relation between LDH-A expression and clinicopathological characteristics including menopause, tumor size, node involvement, differentiation and pathological subtypes classified by estrogen receptor (ER), progesterone receptor (PR) and Her-2. LDH-A expression was found to be correlated significantly with breast cancer size and independent with other clinicopathological factors. LDH-A silencing in breast cancer cell lines MDA-MB-231 and MCF-7 resulted in an inhibited breast cancer cell proliferation, elevated intracellular oxidative stress, induction of mitochondiral pathway apoptosis and limited tumorigenic ability, indicating that LDH-A inhibition might offer a promising therapeutic strategy for breast cancer. SS is historically recommended to invigorate blood circulation and has been prescribed to treat diseases relating to blood stasis syndromes including menstrual abnormalities, anemia, numbness of the limbs, arthritis and cancer, etc. Our following study revealed that SS aqueous extracts could significantly inhibited breast cancer LDH-A expression and activity in both in vitro and in vivo models built by MDA-MB-231 and MCF-7 cell lines. Bioactivity guided fractionation based on LDH-A activity, apoptosis and LDH-A expression further identified epigallocatechin (EGC) as the key compound responsible for the inhibited LDH-A expression. Mechanistic studies found that the inhibitory effect of EGC on LDH-A expression was mainly through promoting Hypoxia inducible factor-1α (HIF-1α) proteasome degradation rather than inhibiting transcription activity, which might be correlated with decreased binding between HIF-1α and Hsp90. Consistent with in vitro findings, EGC was also demonstrated effecitve in suppressing breast cancer growth in vivo correlating to down-regulation of LDH-A, HIF-1α and triggerment of apoptosis. This study provides preliminary laboratory evidences for applying SS in breast cancer therapy. However, further research is needed to evaluate its metabolism, the synergistic effects with chemotherapeutic agents and clinical efficiency.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B48329423-
dc.subject.lcshPlant bioactive compounds.-
dc.subject.lcshSpatholobus - Therapeutic use.-
dc.subject.lcshLactate dehydrogenase.-
dc.subject.lcshBreast - Cancer - Treatment.-
dc.titleIdentification and characterization of bioactive compounds in Spatholobus suberectus targeting on LDH-A in breast cancer-
dc.typePG_Thesis-
dc.identifier.hkulb4832942-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineChinese Medicine-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4832942-
dc.date.hkucongregation2012-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats