p53 Tumour Suppressor Genes Activated By Herbs and Supplements


Cells are incessantly bombarded by an assortment of environmental and intrinsic factors that cause cellular damage. Although mild damage is often reparable, extensive damage poses a potential oncogenic danger. In the latter case, the benefit of the organism calls for the eradication of the potentially life-threatening cells, which often is achieved through activation of an apoptotic cell death program. Thus, the cell is continually faced with an agonizing choice: repair and live, or die (Aylon & Oren 2007).
Mutations of p53, a tumor suppressor gene, are known to be involved in the pathogenesis of a number of neoplasms. Findings support the hypothesis that p53 mutations are homogeneous throughout a tumor and may thus be a more useful diagnostic and prognostic indicator than the expression of p53, which does not reliably correlate with p53 mutations.
P53 has many anticancer mechanisms, and plays a role in apoptosis, genetic stability, and inhibition of angiogenesis. In its anti-cancer role, p53 works through several mechanisms:
1. It can activate DNA repair proteins when DNA has sustained damage.
2. It can induce growth arrest by holding the cell cycle at the G1/S regulation point on DNA damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle).
3. It can initiate apoptosis, the programmed cell death, if DNA damage proves to be irreparable.
Scutellaria barbata, a traditional Chinese herbal medicine native to southern China, is widely used as an anti-inflammatory and a diuretic in China. Extracts of Scutellaria barbata have been shown to have in vivo growth inhibitory effects on a number of cancers such as S180 mouse sarcoma, U14 cervical carcinoma, solid hepatoma, etc. The extract of Scutellaria barbata on human lung cancer cells, A549, exhibited a marked growth inhibitory effect in a dose-dependent manner. The IC50 was approximately 0.21 + 0.04 mg/ml.
Apoptosis of A549 cells induced by Scutellaria barbata was analyzed by Annexin-V staining and demonstrated that treated cells with 0.5 mg/ml Scutellaria barbata extract for 48 hours resulted in a rate of cell apoptosis of 57.67%. The cDNA microarray experiment was performed to characterize the mechanism of Scutellaria barbata induced killing and found that two genes related to cell response to DNA damage, GADD45A and GIP, decreased dramatically. A total of 20 cell cycle genes were found to have changed after treatment indicated that the cell cycle was widely involved in the Scutellaria barbata treatment. Some enzyme activity (STK12,DUSP5 and TOPK), cell signal transduction (GIP, BMP2), nucleic acid binding (ATF3,HNRPD and SMARCF1)were also found to be affected (Yin et al 2004).
Herba Scutellaria barbatae, was cytotoxic to 100% (11 of 11) of actively proliferating ovarian lines tested and 50% (2 of 4) of actively proliferating breast cell lines tested. Confluent cultures were resistant to killing by herb, whereas subconfluent cultures were sensitive. Resistant proliferating cell lines expressed higher levels of bcl2 (Powell et al 2003).

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