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Garcinol (cancer research)
DNA damage may be induced by environmental causes or natural biological functions and may lead to the formation of cancerous cells. Introducing a body to carcinogenic material or ionizing radiation (IR) may lead to single strand or double-strand breaks within the DNA helix. Double strand breaks (DSBs) occur when both strands of the DNA helix has been severed and are especially dangerous to the body due to their ability to cause genome rearrangement. One pathway that prefers to repair double strand breaks induced by irradiation is the Non-Homologous End Joining (NHEJ). The NHEJ Pathway operates by rejoining the broken strands through a process called ligation. For the NHEJ pathway to occur, chromatin remodeling must take place, a process in which the histone-DNA complex, otherwise known as a nucleosome, is rearranged.

Histone Acetyltransferase Inhibition
The process of chromatin remodeling involves several enzymes that assist in the reformation of the nucleosome. Nucleosomes are DNA segments that are tightly-wounded around histone proteins which function as a DNA packaging system. One class of enzymes that is involved in the signaling of chromatin remodeling is called histone acetyltransferases. Histone acetyltransferases add acetyl groups to histones, allowing the tightly bound histone complex to relax and allow other proteins to act on the DNA. If histone acetyltransferases are inhibited, then damaged DNA may not be repaired, eventually leading to cell death. Scientists believe that controlling the chromatin remodeling process within cancer cells may provide a novel drug target for cancer research. Attacking this specific enzyme within cancer cells will cause them to undergo apoptosis more readily due to their high accumulation of DNA damage. One such inhibitor of histone acetyltransferase is called garcinol. Garcinol is found within the rinds of the Garcinia indica fruit, otherwise known as mangosteen. To explore the physiological effects of garcinol on histone acetyltransferase, researchers utilized HeLa cells, named after the woman whose cancerous cells gave rise to the first immortal cell line. The cells underwent irradiation, creating double strand breaks within the DNA, and garcinol was introduced into the cells to see if it influences the DNA damage response. If the garcinol is successful at inhibiting the Non Homologous End Joining pathway, then it may serve as a radiosensitizer, a molecule that increases the sensitivity of cells to radiation damage.

Results
Researchers from Japan that garcinol effectively inhibits histone acetyltransferase, disallowing the reformation of the histone complexes and preventing the NHEJ pathway to occur. Inhibition of the histone acetyltransferase radiosensitizes the HeLa cells and allows them to become more susceptible to irradiation and the formation of double strand breaks. This was demonstrated by introducing garcinol into irradiated cells. As concentrations of garcinol increased, cell viability decreased suggesting that garcinol does indeed have adverse effects to irradiated and DNA-damaged cells.

Significance
Increasing the radiosensitivity of cancerous cells may increase the rate at which cancerous cells die. It is possible that with its effective radiosensitizing function, garcinol may be added to the wide variety of existing cancer treatments. Results show that garcinol does not have any adverse effects on humans. This is supported by the experimental results3. Additionally, previous studies show that there have been no severe side effects within rats that have been treated with garcinol results and because garcinol is currently utilized within weight loss supplements and have shown no adverse effects. The results also suggests that because it does not inhibit the cell cycle yet still manages to inhibit DNA damage repair systems including the NHEJ pathway, it shows potential as a radiosensitizer. However, the cell lines used to test produce these results came from epithelial cells, a rapid dividing cell group that lines the cavities of your body. Because radiotherapy shows preference to rapidly dividing cells, it is possible that the physiological effects of garcinol are selective towards the cell type (epithelial cells) rather than it being specific to cancerous cells. Further studies must be performed to confirm whether or not garcinol is specific to cancer cells.