Aminolaevulinic acid-induced photodynamic therapy: cellular responses to glucose starvation

Abstract

Photodynamic therapy is a cancer treatment based on the interaction of light, oxygen and a photosensitiser. Protoporphyrin. IX is an endogenous photosensitiser derived from the pro-drug aminolaevulinic acid. Tumours contain areas of hypoxia and hypoglycaemia. Tumour cells adapt to these conditions by stress protein induction which may induce resistance to cancer therapies. The effect of chronic hypoglycaemia on sensitivity to aminolaevulinic acid-induced photodynamic therapy in vitro was studied in MCF-7, human breast cancer cells. Following chronic exposure to 0, 1 or 25 mM, glucose, cells were treated with aminolaevulinic acid and the generation of intracellular protoporphyrin. IX measured by spectrofluorimetry. Aminolaevulinic acid-induced photodynamic therapy sensitivity was compared between cells following chronic exposure to 0, 1 or 25 mM glucose. Percentage cell survival was determined by clonogenic assay. Cells cultured in low glucose generated higher levels of protoporphyrin IX compared to standard glucose medium (0 mM glucose: 0.88610 75 ng cell 71 , 1 mM: 0.86610 75 ng cell 71 , 25 mM: 0.605610 75 ng cell 71 , P50.05). However, photodynamic therapy sensitivity was reduced in glucose deprived cells (0 mM glucose: 61% survival, 1 mM: 80.5% and 25 mM: 39.6%, P50.05). Chronic exposure to low glucose induces photodynamic therapy resistance despite increased intracellular concentrations of protoporphyrin IX and may reflect cellular adaptation to chronic glucose deprivation.

Glucose deprivation increases nuclear DNA repair protein Ku and resistance to radiation induced oxidative stress in human cancer cells

“…Recent studies have indicated that nutrient deprivation, particularly glucose, may play a major role in tumor cell tolerance to a generally oxidative stress environment in solid tumors (23, 24). It has been demonstrated that chronic exposure to low glucose have caused photo dynamic therapy (PDT) resistance in breast cancer cells (25). Glucose regulated protein GRP78 is believed to play a major role in the survival of cancer cells during hypoxia, low pH and stress.…”

“…Although the role of prolonged low glucose exposure in PDT resistance has been demonstrated in breast cancer cells (25), the impact of short-term low glucose exposure has not been studied for any kind of cancer therapy. It is important to determine the impact of short-term exposure to low glucose prior to therapy since it is likely that short term exposure to low glucose and low oxygen may also occur in solid tumors.…”

Breast cancer as photodynamic therapy target: Enhanced therapeutic efficiency by overview of tumor complexity

“…In this sense, the effect of chronic hypoglycemia on sensitivity to aminolaevulinic acid-induced PDT in vitro was studied in human breast cancer cells. It was shown that photodynamic therapy sensitivity was reduced in glucose-deprived cells [47] (Figure 1). Additionally, tumors, due to their abnormal vasculature, are characterized by a more acidic environment compared to their surrounding normal tissues.…”

“…As a result, it is possible to find a concentration gradient of the drug within the breast TME between the tumor tissue and the normal surrounding tissue. By injecting glucose, it is possible to further selectively reduce the extracellular pH value of tumors [49] , and to make tumor cells more sensitive to PDT treatment [47] . This will, in 905 December 10, 2014|Volume 5|Issue 5| WJCO|www.wjgnet.com PDT is one of the alternative methods for breast cancer treatment and involves: (1) administration of a photosensitizer (PS), which is internalized into either tumor cells or surrounding vasculature; (2) local irradiation at a wavelength corresponding to the absorbance peak of the PS; and (3) light activation of the PS, which promotes cell death mainly by apoptosis.…”

Effect of Oil-in-Water Emulsions on 5-Aminolevulinic Acid Uptake and Metabolism to PpIX in Cultured MCF-7 Cells

“…The cells are of human origin and presumed to conserve some differentiated mammary epithelial cell function (22), that is, potentially the PEPT2 transporter. MCF-7 cells have previously been used in studies with photosensitizers (23). In particular, the effect which different oil/water (o/w) emulsions have on the amount of PpIX formed was evaluated.…”