Radiosensitizing effect of 5‑aminolevulinic acid in colorectal cancer in�vitro and in�vivo

Abstract

The radiosensitizing effect of 5-aminolevulinic acid (5-ALA) has been demonstrated in glioma and melanoma in a number of studies. Enhancing the radiosensitivity of colorectal cancer may improve survival rates and lessen adverse effects. The present study assessed the radiosensitizing effect of 5-ALA in colorectal cancer using the human colon cancer cell line HT29 in vitro and in vivo . In vitro , cells were pretreated with 5-ALA and exposed to ionizing radiation. Cells pretreated with or without 5-ALA were compared using a colony formation assay. In vivo , HT29 cells were implanted into mice subcutaneously and subsequently exposed to ionizing radiation. 5-ALA was administrated by intraperitoneal injection. Subcutaneous tumors treated with or without 5-ALA were compared. Single-dose and multi-dose irradiations were applied both in vitro and in vivo . Cells exposed to multi-dose irradiation and pretreated with 5-ALA in vitro had a significantly lower surviving fraction compared with cells without 5-ALA pretreatment. Following multi-dose irradiation in vivo , the volume of the subcutaneous tumors treated with 5-ALA was significantly lower compared with that of tumors without treatment. These results suggest that radiotherapy with 5-ALA may enhance the therapeutic effect in colon cancer.

DNA Strand Break Properties of Protoporphyrin IX by X-ray Irradiation against Melanoma

“…A series of studies on the combination treatment of 5-ALA and ionizing radiation has been conducted by some research groups, and 5-ALA with subsequent intracellular PpIX accumulation has been found to increase kilo electron volt (KeV) or mega electron volt (MeV) irradiation cytotoxicity in a variety of contexts using mouse models of melanoma, glioma, colon cancer, etc. [5][6][7][8][9][10][11][12][13][14][15]. PpIX expression enhances ROS generation, which increases cellular DNA damage.…”

“…The total clinical radiation dose is limited to a threshold value to avoid causing any damage to normal cells [3,4]. To overcome this issue, a series of studies on the combination treatment of 5-aminolevulinic acid (5-ALA) and ionizing radiation have been conducted by some research groups using mouse models of melanoma, glioma, and colon cancer [5][6][7][8][9][10][11][12][13][14][15]. It is known that 5-ALA administration specifically results in the accumulation of protoporphyrin IX (PpIX) in cancer cells by inhibiting the conversion PpIX to heme [16,17].…”

A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen

“…Malignant cell radiosensitization by selective 5-ALA uptake was also seen in preclinical models of cancers other than glioma, for example, colon, melanoma, and prostate [22,24,26]. This radiosensitization is thought to occur through mitochondrial damage mediated by PpIX, a metabolic product of 5-ALA that captures light or keV or MeV photons and transfers the energy to O 2 to then generate singlet oxygen.…”

“…Interestingly, 5-ALA with subsequent intracellular PpIX accumulation also increases keV or MeV irradiation cytotoxicity in a variety of contexts [22][23][24][25][26][27][28][29][30][31][32][33]. A robust, detailed physics-based explanation for this is currently lacking, but ample preclinical data attest to the basic mechanism of PpIX interacting with keV photons to generate cytotoxicity greater than the same irradiation given without 5-ALA where 5-ALA serves as a radiosensitizer.…”

“…A robust, detailed physics-based explanation for this is currently lacking, but ample preclinical data attest to the basic mechanism of PpIX interacting with keV photons to generate cytotoxicity greater than the same irradiation given without 5-ALA where 5-ALA serves as a radiosensitizer. These twelve recent studies drive the imperative to study 5-ALA during the irradiation of DIPG [22][23][24][25][26][27][28][29][30][31][32][33].…”