Safety evaluation of low level light therapy on cancer cells

OBJECTIVE: Low level light therapy (LLLT) is being widely used in wound healing and pain relief, and its use is expected to be expanded rapidly to treatment of other disorders as well in a foreseeable future. However, before its expansion, the fear that LLLT could initiate or promote metastasis must be addressed thoroughly. As an initial effort towards this end, the current study evaluates the safety of LLLT in vitro using two different human cancer cell lines (Michigan Cancer Foundation-7 (MCF-7) and Jurkat E6-1) by determining the viability of cells after low level light (LLL) application while treatment under anti-cancer chemotherapeutic drugs (5-fluorouracil (5-FU) and cisplatin) separately on each cell line. METHODS: Two human cancer cell lines (MCF-7 and Jurkat E6-1) were cultured throughout the experiments. Two different anti-cancer chemotherapeutic drugs (5-FU and cisplatin) were used to treat both cell lines. The half maximal inhibitory concentration (IC50) of each drug on each cell line was determined by treating each cell line with varying concentrations of each drug. A total of 3 or 4 trials were done for each cell line with each drug, and the range of concentration was narrowed closer to the IC50 value at each successive trial. Once the IC50 concentrations were determined, each cell line was treated with 808 nm LLL at varying energy densities in a single dose using a light emitting diode (LED) source both in the absence and the presence of each drug at one IC50. A total of 3 or 5 trials were done for each cell line with each drug, and for each trial, six different energy densities ranging from 0 J/cm2 (control) to 10 J/cm2 were applied. The energy densities were varied for each trial with control always being used. After application of LLL, the viability of cells was determined, and three different 1-way ANOVA (Analysis of Variance) analyses were done to compare the viability of cells at each energy density to that of control. RESULTS: The IC50 of 5-FU in MCF-7 and Jurkat E6-1 cells was determined as 70 µM and 20 µM respectively. The IC50 of cisplatin in MCF-7 and Jurkat E6-1 cells was determined as 17 µM and 7 µM respectively. No significant difference (P > 0.05) in the viability of MCF-7 cells was observed between each group treated with different energy density of LLL and control group (0 J/cm2) both in the absence and the presence of 5-FU at IC50 (70 µM). No significant difference (P > 0.05) in the viability of MCF-7 cells was observed between each group treated with different energy density of LLL and control group (0 J/cm2) both in the absence and the presence of cisplatin at IC50 (17 µM). No significant difference (P > 0.05) in the viability of Jurkat E6-1 cells was observed between each group treated with different energy density of LLL and control group (0 J/cm2) both in the absence and the presence of 5-FU at IC50 (20 µM). However, a significant increase (0.01 < P < 0.05) in the viability of cells was observed when treating Jurkat E6-1 cells with 10 J/cm2 of LLL in the presence of cisplatin at IC50 (7 µM) compared to control group (0 J/cm2). Except for the comparison mentioned previously, no significant difference in the viability of Jurkat E6-1 cells was observed between each group treated with different energy density of LLL and control group (0 J/cm2) both in the absence and the presence of cisplatin at IC50 (7 µM). No definite trend in the viability of cells was observed with increasing energy density of LLL for each cell line either in the absence of the presence of each drug at IC50. CONCLUSIONS: The application of LLL at 808 nm with energy densities ranging from 0.1 J/cm2 to 10 J/cm2 under an LED source did not induce cell proliferation or death compared to control (0 J/cm2) for each cell line in the absence or the presence of each drug, and no definite trend was observed with increasing energy density. The study suggests that LLLT at these parameters may be safe to use on cancer patients, but further studies on different cancer cell lines and animal models with different parameters (wavelength, energy density, dosage) of LLL are warranted

Effects of squeezing on quantum nonlocality of superpositions of coherent states

We analyze effects of squeezing upon superpositions of coherent states (SCSs) and entangled coherent states (ECSs) for Bell-inequality tests. We find that external squeezing can always increase the degrees of Bell violations, if the squeezing direction is properly chosen, for the case of photon parity measurements. On the other hand, when photon on/off measurements are used, the squeezing operation can enhance the degree of Bell violations only for moderate values of amplitudes and squeezing. We point out that a significant improvement is required over currently available squeezed SCSs in order to directly demonstrate a Bell-inequality violation in a real experiment.Comment: 7 pages, 4 figures, accepted for publication in Phys. Rev.

Testing Bell inequalities with photon-subtracted Gaussian states

Recently, photon subtracted Gaussian states (PSGSs) were generated by several experimental groups. Those states were called "Schr\"odinger kittens" due to their similarities to superpositions of coherent states (SCSs) with small amplitudes. We compare the ideal SCSs and the PSGSs for experimental tests of certain types of Bell inequalities. In particular, we analyze the effects of the key experimental components used to generate PSGSs: mixedness of the Gaussian states, limited transmittivity of the beam splitter and the avalanche photodetector which cannot resolve photon numbers. As a result of this analysis, the degrees of mixedness and the beam splitter transmittivity that can be allowed for successful tests of Bell inequalities are revealed.Comment: 9 pages, 7 figures, to be published in Phys. Rev.

Faithful test of non-local realism with entangled coherent states

We investigate the violation of Leggett's inequality for non-local realism using entangled coherent states and various types of local measurements. We prove mathematically the relation between the violation of the Clauser-Horne-Shimony-Holt form of Bell's inequality and Leggett's one when tested by the same resources. For Leggett inequalities, we generalize the non-local realistic bound to systems in Hilbert spaces larger than bidimensional ones and introduce an optimization technique that allows to achieve larger degrees of violation by adjusting the local measurement settings. Our work describes the steps that should be performed to produce a self-consistent generalization of Leggett's original arguments to continuous-variable states.Comment: 8 pages, 6 figures, to be published in Phys. Rev.

Testing non-local realism with entangled coherent states

We investigate the violation of non-local realism using entangled coherent states (ECS) under nonlinear operations and homodyne measurements. We address recently proposed Leggett-type inequalities, including a class of optimized incompatibility ones and thoroughly assess the effects of detection inefficiency.Comment: 7 pages, 6 figures, RevTeX4, accepted for publication in Phys. Rev.