Hyperthermia switches glucose depletion-induced necrosis to apoptosis in A549 lung adenocarcinoma cells.
Both cellular and clinical studies have shown that hyperthermia is one of the most potent sensitizers for the action of ionizing radiation. Although hyperthermic improvement in clinical outcome is suggested to be linked to its ability to induce cell cycle arrest and apoptosis, and to activate the immune system and to cause increases in blood flow and tumor oxygenation, the mechanism behind this is still unclear. Previously, we demonstrated that glucose deprivation (GD), a common characteristic of the tumor microenvironment, induced necrosis, which is implicated in tumor progression and aggressiveness, through the production of reactive oxygen species (ROS) in A549 lung carcinoma cells. We examined the effects of heat shock on ROS production and necrosis in response to GD. Here we show that mild, but not harsh, heat shock prevented GD-induced necrosis and switched the cell death mode to apoptosis in A549 cells through the ERK1/2 pathway that could suppress GD-induced CuZnSOD release and ROS production. These results demonstrate that contrary to severe heat shock, mild heat shock has the ability to decrease oxidative stress in cells, thereby causing the cell death mode switch from tumor promoting necrosis to tumor suppressive apoptosis, which may contribute to its anti-neoplastic activities.
Han
Song Iy
SI
Research Center for Resistant Cells, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Duong
Hong-Quan
HQ
Choi
Jeong Eun
JE
Lee
Tae-Bum
TB
Kim
Cho Hee
CH
Lee
Su Yeon
SY
Jeon
Hyun Min
HM
Shin
Sung-Heui
SH
Lim
Sung-Chul
SC
Kang
Ho Sung
HS
D000230:Adenocarcinoma / Q000473:pathology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005335:Fever of Unknown Origin / Q000150:complications; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D006979:Hyperthermia, Induced; D008175:Lung Neoplasms / Q000473:pathology*; D009336:Necrosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000502:physiology
D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose