Cancer cells could predominantly produce energy by glycolysis even in the presence of oxygen. This alternative metabolic characteristic is known as the “Warburg Effect.” Although the exact mechanisms underlying the Warburg effect are unclear, recent progress indicates that glycolytic pathway of cancer cells could be a critical target for drug discovery. With a long history in cancer treatment, traditional Chinese medicine (TCM) is recognized as a valuable source for seeking bioactive anticancer compounds.

It  is  well  known  that  malignant  cells  have  accelerated  glucose  uptake  and  metabolism  in  order  to  maintain  their  fast  proliferation rates. With the increased influx of glucose into cancer cells, glycolysis is facilitated through a coordinated regulation of metabolic enzymes and pyruvate consumption.

Shifting from mitochondrial oxidative phosphorylation to glycolysis and other pathways such as pentose phosphate pathway (PPP) and denovo fatty acid synthesis in the breast tumor  provides  not  only  energy  but  also  the  materials  needed  for  cell  proliferation.  Glucose  augmentation  in  tumor  cells  can  be  due  to  the  elevated  level  of  glucose  transporter (GLUT) proteins, such  as  the  over-expression  of  GLUT 1 and  expression  of  GLUT 5 in  breast  cancers.  Moreover, other  factors  such  as  hypoxia-inducible  factor-1 (HIF-1), oestrogen  and  growth  factors  are  important  modulators  of  glucose  metabolism  in  the  progression  of  breast  carcinomas.  

Therapies  targeting  at  the  glycolytic  pathway, fatty  acid  synthesis  and  GLUTs  expression  are  currently  being  investigated. Restoring tumor cells to its normal glucose metabolic state would endow tumor specific and accessible treatment that targets glucose metabolism 

Source

Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy. https://www.researchgate.net/publication/228469933_Glucose_Metabolism_in_Breast_Cancer_
and_its_Implication_in_Cancer_Therapy [accessed Jun 6, 2016].

Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. HSC is composed of Cornus officinalis, Fructus crataegi, Millettia dielsiana, Pericarpium Citri  reticulatae, Radix Ginseng rubra, Rehmannia glutinosa, Radix astragali, Radix Paeoniae lactiflorae, Semen coicis, Rhizoma anemarrhenae, and Rhizoma Ligustici chuanxiong

In this study, Li et al., (2015) investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. 

Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. 

Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. 

The analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment  with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. The data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage.

Catalpol (a main bioactive component in the roots of Rehmannia glutinosa) decreased plasma malondialdehyde (MDA) intestinal 8-hydroxydeoxyguanosine (8-OHdG) levels and increased plasma endogenous antioxidants and peripheral white blood cells and platelets in vivo, which suggested that catalpol possessed notable radio-protective activity by reducing reactive oxygen species (ROS) [1].  The  components  of Cornus officinalis showed significant free radical-scavenging activity and inhibitory effects on melanogenesis induced by radiation [2]. Millettia dielsiana had an anti-inflammatory effect, decreasing NO production [3]. The extracts of Fructus crataegi were reported to have a radio-protective effect with antioxidant activity [4,5] and protected lymphocytes from the effects of radiation [6]. Citri reticulatae pericarpium possessed various pharmacological effects involved in antioxidant ability against hydroxyl-induced DNA damage [7]. Anemarrhenae Rhizoma showed various bioactivities, such as anti-tumor, anti-oxidation, anti-microbial, anti-virus, anti-inflammation, anti-osteoporosis, anti-skin aging and damage effects, as well as other activities [8]. The combination of different types of medical herbs above in HSC can benefit from each other with different roles in the formula, and ultimately gain the goal of enhancing efficacy, which caters to the core thinking of traditional Chinese medicine theory. 

Source:

Li Jz, Xu J, Xu Wh, et al. Int. J. Mol. Sci. 2015, 16, 18938-18955; doi:10.3390/ijms160818938

References

1. Lagadec, C.; Vlashi, E.; Alhiyari, Y.; Phillips, T.M.; Bochkur Dratver, M.; Pajonk, F. Radiation-induced Notch signaling in breast cancer stem cells. Int. J. Radiat. Oncol. Biol. Phys. 2013, 87, 609–618.

2. Nawa, Y.; Endo, J.; Ohta, T. The inhibitory effect of the components of Cornus officinalis on melanogenesis. J. Cosmet. Sci. 2007, 58, 505–517. 

3. Ye, H.; Wu, W.; Liu, Z.; Xie, C.; Tang, M.; Li, S.; Yang, J.; Tang, H.; Chen, K.; Long, C.; et al. Bioactivity-guided isolation of anti-inflammation flavonoids from the stems of Millettia dielsiana Harms. Fitoterapia 2014, 95C, 154–159. 

4. Leskovac, A.; Joksic, G.; Jankovic, T.; Savikin, K.; Menkovic, N. Radioprotective properties of the phytochemically characterized extracts of Crataegus monogyna, Cornus  mas  and  Gentianella austriaca on human lymphocytes in vitro. Planta Med. 2007, 73, 1169–1175.

5. Hosseinimehr, S.J.; Azadbakht, M.; Mousavi, S.M.; Mahmoudzadeh, A.; Akhlaghpoor, S. Radioprotective effects of hawthorn fruit extract against γ irradiation in mouse bone marrow cells. J. Radiat. Res. 2007, 48, 63–68.

6. Hosseinimehr, S.J.; Mahmoudzadeh, A.; Azadbakht, M.; Akhlaghpoor, S. Radioprotective effects of hawthorn against genotoxicity induced by γ  irradiation  in  human  blood  lymphocytes.  Radiat. Environ. Biophys. 2009, 48, 95–98.

7. Li, X.; Huang, Y.; Chen, D. Protective effect against hydroxyl-induced DNA damage and antioxidant activity of citri reticulatae pericarpium. Adv. Pharma. Bull. 2013, 3, 175–181.

8. Wang, Y.; Dan, Y.; Yang, D.; Hu, Y.; Zhang, L.; Zhang, C.; Zhu, H.; Cui, Z.; Li, M.; Liu, Y. The genus Anemarrhena Bunge: A review on ethnopharmacology, phytochemistry and pharmacology.

J. Ethnopharmacol. 2014, 153, 42–60.