Blue light irradiation inhibits the growth of colon cancer and activation of cancer‑associated fibroblasts

Abstract

Irradiation with a specific wavelength of light using light-emitting diodes (LEDs) has various effects on cells and organisms. Recently, the antitumor effects of visible blue light on tumor cells were reported; however, the mechanism and effects on the tumor microenvironment remain unclear. Human colon cancer cells (HCT-116) were injected into the rectal wall of nude mice. Tumors were irradiated with a 465-nm LED light at 30 mW/cm 2 for 30 min. Tumor volumes and the expression levels of opsin 3 (Opn3), autophagy-related factors, cancer-associated fibroblast (CAF) markers, and programmed cell death 1-ligand (PD-L1) were measured. Additionally, human intestinal fibroblasts were cultured in HCT116-conditioned medium (CM) to prepare CAFs. CAFs were divided into an LED group and a control group, and the effect of the LED light on CAF activation in colon cancer cells was examined. Irradiation with blue LED light suppressed tumor growth; Opn3 expression was localized to the cell membrane in the LED group. Irradiated tumors exhibited increased autophagy-related gene expression. Furthermore, in the LED group, TGF-β and α-SMA expression levels in the fibroblasts were decreased. Regarding CAFs, α-SMA and IL-6 expression levels were decreased in the LED group. HCT-116 cells cultured in CAF-CM with LED irradiation showed no enhanced migration or invasion. In the HCT-116 cells cultured in CM of CAFs irradiated with LED, the relative increase in PD-L1 expression was lower than that noted in the CAF-CM without LED irradiation. Blue LED light may have a direct antitumor effect on colon cancer and also an inhibitory effect on CAFs.

Highly effective synthesis of mercapto-functionalized cubic silsesquioxanes as the first step in designing advanced nano-delivery systems

“…It is particularly interesting in the context of literature reports indicating the use of blue light in cancer therapy. 36…”

Blue light induces apoptosis and autophagy by promoting ROS‐mediated mitochondrial dysfunction in synovial sarcoma

“…All previous studies that we have been able to find used high‐power BL irradiation for 30 min to 24 h to investigate the effects on cancer cells. 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 The concept of our study, with an eye toward initial clinical application, was to implant small wireless LEDs in the body and continuously irradiate the tumor. Therefore, it was necessary to develop an experimental model in which BL was irradiated at the lowest possible power for a long period of time, for example, up to 72 h. Recent studies have reported remarkable progress in the development of small wireless LEDs, and data from mouse animal experiments using small wireless LEDs in the fields of photodynamic therapy 41 and photoimmunotherapy 42 suggest the potential for these devices in BL therapy applications.…”

“…We also found that continuous irradiation of SS cells with a very low‐power BL source showed marked antitumor effects. All previous studies that we have been able to find used high‐power BL irradiation for 30 min to 24 h to investigate the effects on cancer cells 9–22 . The concept of our study, with an eye toward initial clinical application, was to implant small wireless LEDs in the body and continuously irradiate the tumor.…”

“…In medicine, phototherapy using LEDs is widely used for several therapeutic targets including acne vulgaris, 4 wound healing, 5 skin rejuvenation, 6 and bacterial and viral infections. 7 , 8 Furthermore, light irradiation at wavelengths ranging from 450 to 495 nm, which human eyes perceive as blue, has been shown to have antitumor effects on various cancer cells, including melanoma, 9 , 10 lymphoma, 11 colon cancer, 12 , 13 , 14 , 15 leukemia, 16 pancreatic cancer, 17 and osteosarcoma. 18 Therefore, blue light (BL) from LEDs is expected to become a novel non‐invasive therapeutic option in cancer treatment.…”

Immunoactivation by Cutaneous Blue Light Irradiation Inhibits Remote Tumor Growth and Metastasis

“…13,14 Our previous works also show that blue light irradiation can regulate the tumor immune microenvironment via NF-κB signaling pathway and promote the secretion of immunoactive cytokines in skin. 11,15,16 As the main source of ROS, mitochondria have been reported to be important organelle in the "photobiomodulation" process induced by blue light. 17,18 The respiratory complex of the mitochondrial electron transport chain contains iron porphyrin proteins, which are capable of specific absorption for shortwavelength light.…”