TABLE 1.
Study characteristics of the in vitro studies investigating the effect of PBMT on cancer cell lines
| Author (Ref.) | Year | Cell type | PBM device | Wavelength | Fluence | Exposition time (sec) | Application protocol | Cell viability /proliferation |
|---|---|---|---|---|---|---|---|---|
| Marchesini 61 | 1989 | Colon carcinoma (HT29), Breast carcinoma (MCF7), Malignant melanoma (M14 and JR1) | Argon LD | N.S | 4.2 and 150 kJ/m2 | N.S. | Single application | Increases tumor cell culture growth |
| Tsai 50 | 1991 | Glioma cell (C6) |
four different types: ‐ CO2 ‐ Argon ‐ HeNe ‐ GaAs |
‐ 488–512 nm ‐ 632.8 nm ‐ 904 nm |
‐ 0.4–22 J/cm2 ‐ 1.1–11 J/cm2 ‐ 2.7–326 mJ/cm2 ‐ 9–380 mJ/cm2 |
‐ 0.1 to 20 s ‐ 0.5 to 5 s ‐ 1 to 120 s ‐ 9 to 350 s |
Single application |
‐ He‐Ne laser induced a dose‐related biostimulatory effect ‐No dose related biostimulatory effect was noted after GaAS laser irradiation |
| Schaffer 49 | 1997 | Human squamous carcinoma cell lines of the gingival mucosa (ZMK) | LD | 805 nm | 2–20 J/cm2 | N.S. | Single application | ZMK cells showed a decreased of mitotic index at 4 and 20 J/cm2 |
| Sroka 51 | 1999 | Skeletal myotubes (C2), normal urothelial cells (HCV29), human squamous carcinoma cells of the gingival mucosa (ZMK1), urothelial carcinoma cells (J82), glioblastoma cells (U373MG), and breast adenocarcinoma cells (MCF7) |
‐Kr+‐laser ‐ Ar+‐laser ‐ Ar+‐pumped tunable dye ‐GaAlAs‐LD ‐Nd:YAG laser |
‐ 410 nm ‐ 630 nm ‐ 635 nm ‐ 640 nm ‐ 805 nm ‐ 1064 nm |
0–20 J/cm2 | N.S. | Single application |
Increased mitotic rate for J82, HCV29 with 410, 635 and 805 nm; C2 with 635 nm Max mitotic rate: J82, HCV29, C2 with 4 and 8 J/cm2 Min mitotic rate: J82, HCV29, C2 with 20 J/cm2 Min mitotic rate for MCF7, U373MG, and ZMK1 with increasing J/cm2; All cell lines with 20 J/cm2 |
| Coombe 59 | 2001 | Human osteosarcoma cell line, (SAOS−2) | GaAlAs LD | 830 nm | 1.7 to 25.1 J/cm2 | N.S. | A single or daily irradiation for a period of 1–10 days | Cellular proliferation or activation was significantly influenced by any of the PBM parameters applied |
| Pinheiro 48 | 2002 | H.Ep.2 cells (SCC type 2) | LD | 635‐ or 670‐nm | 0.04, 0.06, 0.08, 1.2, 2.4, and 4.8 J/cm2 | N.S. | 7 consecutive days at the same daytime | PBM (670 nm) at a dose between 0.04 and 4.8 J/cm2 significantly increased proliferation of H.Ep.2 cells |
| Kreisler 52 | 2003 | Epithelial tumor cells from laryngeal carcinoma | GaAlAs‐LD | 809 nm | 1.96, 3.92, and 7.84 J/cm2 | 75, 150, 300 s | Single application | The irradiated cells demonstrated a higher proliferation rate up to 3 days post‐PBM |
| Liu 61 | 2004 | Human hepatoma cell line (HepG2 and J−5 cells) | GaAlAs‐LD | 808 nm | 5.85 and 7.8 J/cm2 | 90, 120 s | Single application | PBM inhibited the proliferation of HepG2 and J−5 cells |
| Mognato 53 | 2004 | Human epithelial adenocarcinoma (HeLA) and lymphoblast cell line (TK6) | In‐Ga‐As LD | 808–905 nm | 1, 4, 15, 30, and 60 J/cm2 | N.S. | Single application | PBM did not affect HeLa cells at 808 nm but stimulated proliferation at 905 nm and combined wavelengths. TK6 cells were not affected. |
| Werneck 55 | 2005 | H.Ep.2 cells (human SCC larynx) | LD |
685 nm 830 nm |
4 J/cm2 | N.S. | Single application | PBM improved cellular proliferation in cells at 685 nm or 830 nm wavelengths. Top proliferation was detected at 12 h (685 nm) and at 6 h and 48 h (830 nm). |
| De Castro 54 | 2005 | Human oral carcinoma cells 101 | LD |
685 nm 830 nm |
4 J/cm2 | N.S. | One or two applications | PBM (830 nm) increased proliferation at 12 h. The increase was noticeable up to 48 h. No response in cells treated with PBM at 685 nm. |
| Liu 56 | 2006 | Human hepatoma cell line (HepG2 and J−5 cells) | GaAlAs‐LD | 808 nm | 0, 1.95, 3.9, 5.85, 7.8, 9.75, and 11.7 J/cm2 | 0, 30, 60, 90, 120, 150, and 180 s | Single application | PBM at 5.85 and 7.8 J/cm2 inhibited the survival of human HepG2 cells |
| Renno 57 | 2007 | Human osteosarcoma cell line (MG63) | LD |
830 nm 780 nm 670 nm |
0.5, 1, 5, 10 J/cm2 | N.S. | Single application | PBM at 670 nm increased osteosarcoma cell proliferation significantly (at 5 J/cm2). The same was true at 780 nm laser (at 1, 5, and 10 J/cm2), but not after 830 nm PBM |
| Powell 58 | 2010 | Human breast cancer cell line (MCF−7 – adenocarcinoma) and a human melanoma cell line (MDA‐MB−435S/M14) | GaAlAs‐LD |
780 nm 830 nm 904 nm |
0.5, 1, 2, 3, 4, 10, 12, and 15 J/cm2 |
1–3 applications with 24 h in between |
Minimal changes were detected in the growth rates of MDA‐MB−435S (melanoma) cells after a single PBM treatment, regardless of the PBM parameters applied. Increased proliferation of MCF−7 with 1, 2, 4, 10, and 12 J/cm2 at 780 nm and at 0.5, 1, 3, 4 and 15 at 904 nm |
|
| Huang 47 | 2011 | ASTC‐a−1 cells, HeLa cells, human hepatocellular liver carcinoma (HepG2) cells, and African green monkey SV−40‐transformed kidney fibroblast (COS−7) | HeNe LD | 632.8 nm | 20, 40, 80, 120, and 160 J/ cm2 |
1.66, 3.33, 6.66, 10, 13.33 min |
Single application |
PBM increased apoptosis via inactivation of the Akt/GSK3b signaling pathway through ROS production. |
| Al‐Watban 46 | 2012 |
Murine fibrosarcoma (RIF−1) Mouse mammary adenocarcinoma (EMT−6) |
HeNe LD | 632.8 nm | 60, 120, 180, 240, 300, 360, 420, 480, 540, and 600 mJ/cm2 | 16, 32, 48, 64, 80, 96, 112, 128, 144, and 160 s | Three consecutive days | A trend of stimulation, zero‐bioactivation, and inhibition in all cell lines. The ideal biostimulatory dose was 180 mJ/cm2 and bio‐inhibitory doses were from 420–600 mJ/cm2 increasing doses. |
| Schartinger 45 | 2012 | Human oral SCC cell line (SCC−25) | GaAlAs‐LD | 660 nm | N.S. | 15 min | Three consecutive days | PBM led to an increase in the percentage of S‐ phase cells and a decrease in the percentage of G1‐phase cells. PBM induced a pro‐apoptotic effect and no tumor promoting effect. |
| Magrini 44 | 2012 | Human malignant breast cells (MCF−7) | HeNe LD | 633 nm | 5, 28.8, and 1000 mJ/cm2 | 1–16.5 min | Single application | PBM influenced cell metabolism and viability, depending on the fluence, for at least 6.5 days. PBM at 5 mJ∕cm2, had a bio‐inhibitory effect, which led to a decrease in cell metabolism. At 28.8 mJ∕cm2, no proliferation was detected, but there was an increase of the cell metabolism. At 1 J∕cm2, PBM led to an increase of cell metabolism. |
| Murayama 43 | 2012 | Human A−172 glioblastoma cell line | LD | 808 nm | 8, 36, and 54 J/cm2 | 20, 40, and 60 min | Single application | Suppressed proliferation in a fluence‐dependent manner |
| Sperandio 42 | 2013 |
Human dysplastic oral keratinocytes (DOK cell line) Human oral squamous cell carcinoma cell lines (SCC9 and SCC25) |
LD |
660 nm 780 nm |
0, 2.05, 3.07, and 6.15 J/cm2 | N.S. | Single application | PBM changed growth of both cell lines by modulating the Akt/mTOR/CyclinD1 signaling pathway, both up regulating and down regulating depending on the used PBM parameters. |
| Basso 41 | 2014 | Osteosarcoma (Saos2) | InGaAsP LD | 780 nm | 0.5, 1.5, 3, 5, and 7 J/cm2 | 40, 120, 240, 400, and 560 s | Single application | PBM at 0.5 J/cm2 increased cell viability |
| Gomes Henriques 40 | 2014 | Human oral squamous cell carcinoma cell lines (SCC25) | InGaAsP LD | 660 nm | 0, 0.5, 1 J/cm2 | 16 and 33 s | Two applications, 48 hours in between | PBM significantly increased proliferation of SCC25 cells at 1.0 J/cm2. |
| Matsumoto 39 | 2014 | Human Colon cancer cell lines (HT29 and HCT116) | LED |
465 nm 525 nm 635 nm |
N.S. | 10 min | Every 24 h for 5 days | PBM at 465 nm reduced viability of HT29 and HCT116 cells. However, PBM did not change viability of HT29 cells at 525 nm or 635 nm. |
| Tsai 68 | 2015 | Human osteosarcoma cell line (MG−63) | LD | 810 nm | 1.5 J/cm2 | 80 s | Single application before PDT | PBM increases the effect NPe6‐mediated photodynamic therapy via increased ATP synthesis. |
| Obayashi 38 | 2015 | Pancreatic carcinoma cell line (KP4, PK−9, MIA‐PaCa2) | GaAlAs‐LD | 915 nm | N.S. | 3, 5, or 7 min | Single application | Upregulated apoptosis with increasing power and duration of irradiation |
| Cialdai 37 | 2015 | Human breast carcinoma cell lines (MCF−7 and MDA‐MB361) | LD |
808 nm 905 nm |
9 J/cm2 | 10 min | Three consecutive days with | PBMT did not significantly impact the behavior of human breast adenocarcinoma cells, including their clonogenic efficiency |
| Dastanpour 36 | 2015 | Acute myeloid leukemia (AML) cell line (KG−1a) | LD | 810 nm | 5, 10, and 20 J/cm2 | N.S | One to three applications with 48 h in between | PBM significantly increase cell proliferation after two PBM exposures at an energy density of 20 J/cm2. Other PBM parameters did not affect cell proliferation. |
| Crous & Abrahamse 70 | 2016 | Lung cancer stem cells (CSC) isolated from lung cancer cells (A549) | LD | 636 nm | 5, 10, and 20 J/cm2 |
8 min 54 s 17 min 48 s 35 min 36 s |
Single application | PBM increased the cell density due to stimulation of cell proliferation |
| Ramos Silva 34 | 2016 | Human breast cancer cell line (MDA‐MB−231 cells) | GaAlAs LD | 660 nm | 30, 90, 150 J/cm2 | 30, 90, 150 s | Single application | PBM did not influence cell viability. PBM enhanced cell populations in S and G2/M cell cycle phases. PBM led to a decrease in proliferation and increase in senescence. |
| Barasch 33 | 2016 | Normal human lymphoblasts (TK6) Human leukemia cells (HL60) | HeNe LD | 632.8 nm |
0.1, 1, 2, 4, 8,12 J/cm2 |
3, 29, 57, 114, 229, 343 s | Single application | Pre‐radiation exposure to PBM (4.0 J/cm2) followed by 1‐h incubation hindered growth regression in TK6 but not in HL60 cells. PBM made the HL60 cells more susceptible to the killing effects of RT in a dose‐dependent way. Furthermore, exposure of HL60 to PBM alone led to cell death in a dose‐dependent way. |
| Schalch 32 | 2016 | Human lingual squamous cell carcinoma (SCC9) | LD |
660 nm 780 nm |
2.71, 5.43, 8.14 J/cm2 | 12.7, 25.3, 38 s | Single application | PBM of SCC9 cells (4 J/cm2) decreased the pro‐osteoclastogenic potential. |
| Kara 31 | 2017 |
Saos−2 osteoblast‐like cells (ATCC85‐HTB) Human lung carcinoma cells (A549) |
Nd:YAG laser | 1064 nm | N.S. | 0.5 min | Single application | PBM increased cancer cell proliferation, depending on the applied PBM parameters. |
| Djavid 30 | 2017 | Human cervix adenocarcinoma cell line (HeLa) | LD | 685 nm | 0, 5, 10, 20 J/cm2 | N.S. | Single application | PBM at different energy densities (5–20 J/cm2) was not cytotoxic. However, HeLa cells pre‐exposed to 20 J/cm2 showed improved inhibition of colony formation following RT. Enhanced radiosensitivity was related to more DNA damage, and oxidative stress, and radiation‐induced apoptosis and autophagy, |
| Bamps 29 | 2018 | Head and neck cancer (HNSCC) cell lines (SCC154, SQD9, and SCC61) | AsGaAl LD | 830 nm | 1–2 J/cm2 | N.S. | Single application | PBM increased cell proliferation of HNSCC cell lines at 1 J/cm2, while no significant increase was seen after PBM at 2 J/cm2. |
| Schalch 28 | 2018 | Head and neck cancer (HNSCC) cell line (SCC9) | LD |
660 nm 780 nm |
1–6 J/cm2 | 8.4, 16.9, 12.7, 25.3, 38 s | Single application | PBM reduced mitochondrial activity in the SCC9 cells using 11 diverse PBM parameters. PBM at 780 nm (4 J/cm2) was the safest and led to a reduction in cell viability, the induction of apoptosis, and a reduction in the migration capacity of the cancer cells. |
| Diniz 27 | 2019 |
Oral keratinocytes (HaCat) Tongue squamous cell carcinoma cells (SCC25) Upper aerodigestive tract carcinoma cells (HN12) |
GaAlAs LD | 660 nm | 11.7 J/cm2 | 6 s | Single application | PBM led to an increase in sensitivity to cisplatin. PBM could potentiate the effects of cisplatin, leading to increased drug cytotoxicity and enhanced apoptosis. |
| Chen 26 | 2019 | Melanoma cells (B16F10 melanoma cells) | LED |
418 nm 457 nm 630 nm |
0.04,0.07,0.15, 0.22, 0.30, 0.37, 0.45, 0.56, 1.12 | 0, 450, 900, 1800 s | Single application | PBM at 418–457 nm inhibited the growth of the B16F10 melanoma cells and a high energy density had better results. |
| Takemoto 25 | 2019 | Human OSCC cell line (CAL27) | LED | 660 nm | 3, 6 J/cm2, 9, 12, 24, and 36 J/cm2 | N.S. | Three applications | PBM at high doses hindered the progression and number of OSCC colonies without affecting the surrounding stromal fibroblasts. |
| Levchenko 24 | 2019 | HeLa cells | LD | 808 nm | 0.3, 3, 10, and 30 J/cm2 | 6, 60, 200, and 600 s | Single application | PBM (0.3, 3, and 30 J/cm2) induced apoptosis along a gradual increase over time, in contrast to non‐irradiated cells and cells irradiated at 10 J/cm2 |
| Matsuo 23 | 2019 | Squamous cell carcinoma cell line (HSC−3) | LED | 630 nm | N.S. | N.S | Single application | PBM increased the migration ability of HSC−3 cells |
| Kianmehr 22 | 2019 |
HDF cell line Human melanoma cancer cell lines (A375 and SK‐MEL−37) |
LD | 660 nm | 3 J/cm2 | 90 s | Single application | PBM alone is not able to destroy human normal fibroblast and human melanoma cancer cells. PBM in combination with p‐Coumaric acid did not alter the cell viability in human fibroblasts but reduced the cell viability in melanoma cells probably via the apoptosis pathway. |
| Abuelmakarem 21 | 2019 | Colon cancer cell line (Caco−2 cell line) | LD | 660 nm | N.S. | 5 min | Single application | PBM decreased the cell viability. |
| Kiro 64 | 2019 | Isolated CSCs adenocarcinoma MCF7 | LD |
636 nm 825 nm 1060 nm |
5, 10, 20, 40 J/cm2 |
10 min 48 s 20 min 9 s 40 min 21 s 1 h 20 min 30 s |
Single application | PBM increased the cell proliferation and viability of BCCs and BCSCs after being exposed to 5–40 J/cm2 using wavelengths of 636, 825 and 1060 nm. PBM decreased cytotoxicity in both BCCs and BCSCs after treatment with low energy densities. |
| Khorsandi 20 | 2020 |
Breast cancer cell lines (MDA‐MB−231) Melanoma cancer cell line (A375) Human dermal fibroblast cell line (HDF) |
LD | 660 nm | 3 J/cm2 | 90 s | Single application | PBM alone cannot induce cell death in human normal and cancerous cells. PBM in combination with gallic acid (GA) treatment did not alter the cell viability in human normal cells but significantly reduced the survival of cancer cells more than GA alone. |
| Shakibaie 19 | 2020 | Breast cancer cell lines (MCF−7) | LED | 435 and 629 nm | 7.9 and 17.5 J/cm2 | N.S. | Single application | PBM (435 nm) decreased the proliferation and metabolic activity of MCF−7 cells. PBM (626 nm) increased the metabolic activity and proliferation of MCF−7 cells. |
Abbreviations: BCC, breast cancer cell; CSC, cancer stem cell; HNC, head and neck; LD, laser diode; LED, light emitting diode; PBMT, photobiomodulation therapy; ROS, reactive oxygen species; SCC, squamous cancer cell.