Andrographis for lung cancer.
Lung cancer is the leading cause of death from cancer worldwide. The high mortality rate is attributed to its early metastasis, particularly for non small cell lung carcinoma (NSCLC). Despite treatment advances in surgery, chemotherapy and radiotherapy, the overall survival rate is poor.
The mechanisms involved in the metastatic progression of NSCLC are unclear, however increasing evidence points to pro-angiogenic factors in the development of lung tumourigenesis, indicating that the hypoxia-inducible factor-1 alpha (HIF-1[alpha]) plays a role in NSCLC development. Elevated HIF-1[alpha] expression has been reported in NSCLC tissues with poor disease prognosis.
HIF-1[alpha] activates the transcription of many genes, including vascular endothelial growth factor (VEGF). HIF-1[alpha] has been found to target over 100 genes that regulate cellular processes such as glucose metabolism, angiogenesis, proliferation and invasion or metastasis. It is associated with more aggressive phenotypes and therapeutic resistance of tumour cells.
Andrographis paniculata is a herbal medicine widely used in South East Asia for the treatment of fever, cold, inflammation, diarrhoea and other infectious diseases. The main components of this herb are diterpenelactones of which andrographolide is the major component constituting 70% of the plant extract. Recent studies suggest that andrographolide has anticancer and immunomodulatory activities.
This in vitro study examined whether andrographolide could modulate the HIF-1a expression in the NSCLC cell line. Human NSCLC A549 cell lines were cultured in growth media and supplemented with 10% FBS, 2mM glutamine and 100 U/mL penicillin streptomycin mixed antibiotics. All cell cultures were maintained at 37 [degrees]C in a humidified atmosphere of 5% C[O.sup.2].
A standardised extract of andrographolide (purity 98%) was obtained and prepared in a DMSO stock solution, protected from light and stored at -20[degrees]C. Before use the solution was freshly prepared by diluting with a medium to the desired concentration. Controls received the same levels of DMSO.
Time course (0, 15, 30 and 60 min) study showed a significant reduction in HIF-1[alpha] level began at 15 min, through to 60 min, following exposure to 5.0 [micro]M of andrographolide in A549 cells (P[less than or equal to]0.01). The level of HIF-1[alpha]/Ub complex increased faster in the cells treated with andrographolide than that in the untreated cells. This suggests that a post translational mechanism contributed to the andrographolide induced HIF-1[alpha] depletion in A549 cells.
The researchers suggested that the influence of andrographolide on HIF-1[alpha] expression may differ depending on the length of exposure and that the PI3K/ Akt signalling might be responsible for long term regulation of HIF-1[alpha].
In the present study a clear decrease in HIF-1[alpha] expression was found in the andrographolide treated A549 cells, concurrent with a reciprocal increase in VEGF, hydroxy-HIF-1[alpha] and PHD2 expression. The researchers have proposed a possible mechanism for the effects of andrographolide on HIF-1[alpha] signalling in A549 cells and other NSCLC cell lines, suggesting that andrographolide regulated the tumour angiogenetic TGF[beta]1/PHD2/HIF-1[alpha]/VEGF pathway. These findings suggest a role for andrographolide in inhibiting HIF-1[alpha] and VEGF expression that may be important for lung tumour angiogenesis and metastasis. Further studies are needed to clarify the detail pathway of the action of andrographolide.
NB: The CPE questions for this article were included in the previous issue AJMH 23(1) by mistake. They are included again in this issue.
Tessa Finney-Brown MNHAA
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|Publication:||Australian Journal of Medical Herbalism|
|Date:||Jun 22, 2011|
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