Heat shock protein 70 suppresses PS‐341‐induced apoptosis via inhibition of JNK pathway independently of Akt activation in lung cancer cells

Purpose: To investigate the effect of 2,4-dihydropyrano[2,3-c]pyrazole (DHPP) on lung cancer cells, and the associated mechanism.Methods: The effect of DHPP on cell proliferation was measured using sulphorhodamine B (SRB) assay. Apoptosis of cells was determined using Olympus IX71 inverted microscope connected to FITC and rhodamine filters.Results: DHPP significantly suppressed the proliferation of A549 and H1299 cells at doses of 0.5-8.0 μM, but did not affect normal cells (MRC5 and BEAS-2B). In DHPP-treated A549 and H1299 cells, caspase-3 activity was markedly enhanced. At 24 h of treatment with 8.0 μM DUPP, apoptosis in A549 and H1299 cells was increased to 67.89 and 61.35 %, respectively. Phosphorylation levels of JNK-1/2 and p38 in DHPP-treated A549 and H1299 cells were markedly enhanced. The p-ERK-1/2 expressions in DHPP-treated A549 and H1299 cells were suppressed significantly at 24 h. In DHPP-treated A549 and H1299 cells, DCF-fluorescence was increased 10 folds and 8.5 folds, respectively. Pretreatment with FeTMPyP, an antioxidant, effectively alleviated DHPP-induced increase in expressions of p-p38 and p-JNK, and suppression of expression of p-ERK-1/2. In FeTMPyP-pre-treated cells, the DHPPinduced increase in caspase-3 activity was markedly reduced.Conclusion: DHPP selectively inhibits lung cancer cell growth via oxidative stress which subsequently causes cell apoptosis. Moreover, it activates caspase-3 protein and p38/JNK signaling, with simultaneous inactivation of ERK-1/2. Therefore, DHPP has a potential to be developed for the treatment of lung cancer. However; more studies are required to confirm these findings. Keywords: Lung cancer, Anti-oxidant, Apoptosis, Caspase-3, Chemotherapy

Download Full-text

Fas Ligand Enhances Apoptosis of Human Lung Cancer Cells Cotreated with RIG-I-like Receptor Agonist and Radiation

Current Cancer Drug Targets ◽

10.2174/1568009620666200115161717 ◽

2020 ◽

Vol 20 (5) ◽

pp. 372-381

Author(s):

Yoshiaki Sato ◽

Hironori Yoshino ◽

Eichi Tsuruga ◽

Ikuo Kashiwakura

Keyword(s):

Lung Cancer ◽

Cell Surface ◽

Cancer Cells ◽

Fas Ligand ◽

Human Lung ◽

Lung Cancer Cells ◽

Poly I:C ◽

Human Lung Cancer ◽

Human Lung Cancer Cells ◽

Induced Apoptosis

Background: Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play key roles in the antiviral response, but recent works show that RLR activation elicits anticancer activity as well, including apoptosis. Previously, we demonstrated that the anticancer activity of the RLR agonist Poly(I:C)-HMW/LyoVec™ [Poly(I:C)-HMW] against human lung cancer cells was enhanced by cotreatment with ionizing radiation (IR). In addition, cotreatment with Poly(I:C)-HMW and IR induced apoptosis in a Fas-independent manner, and increased Fas expression on the cell surface. Objective: The current study investigated the resultant hypothesis that Fas ligand (FasL) may enhance apoptosis in lung cancer cells cotreated with Poly(I:C)-HMW+IR. Methods: FasL was added into culture medium at 24 h following cotreatment with Poly(I:C)- HMW+IR, after upregulation of cell surface Fas expression on human lung cancer cells A549 and H1299 have already been discussed. Results: FasL enhanced the apoptosis of A549 and H1299 cells treated with Poly(I:C)-HMW+IR. Similarly, IR alone - and not Poly(I:C)-HMW - resulted in the upregulation of cell surface Fas expression followed by a high response to FasL-induced apoptosis, thus suggesting that the high sensitivity of cells treated with Poly(I:C)-HMW+IR to FasL-induced apoptosis resulted from the cellular response to IR. Finally, knockdown of Fas by siRNA confirmed that the high response of treated cells to FasL-induced apoptosis is dependent on Fas expression. Conclusion: In summary, the present study indicates that upregulated Fas expression following cotreatment with Poly(I:C)-HMW and IR is responsive to FasL-induced apoptosis, and a combination of RLR agonist, IR, and FasL could be a potential promising cancer therapy.

Download Full-text

NF-κB Activation Is Related to the Resistance of Lung Cancer Cells to TNF-α-Induced Apoptosis

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.2000.2909 ◽

2000 ◽

Vol 273 (1) ◽

pp. 140-146 ◽

Cited By ~ 35

Author(s):

Jae-Yeol Kim ◽

Seunghee Lee ◽

Bin Hwangbo ◽

Choon-Taek Lee ◽

Young Whan Kim ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Lung Cancer Cells ◽

Tnf Α ◽

Induced Apoptosis

Download Full-text

Elevated levels of intracellular Ca 2+ and apoptosis in human lung cancer cells given heat-shock

International Journal of Hyperthermia ◽

10.1080/02656730210166528 ◽

2003 ◽

Vol 19 (2) ◽

pp. 178-192 ◽

Cited By ~ 5

Author(s):

T. Hashimoto ◽

M-A. Shibata ◽

Y. Ito ◽

K.-I. Nakao ◽

S. Sasaki ◽

...

Keyword(s):

Lung Cancer ◽

Heat Shock ◽

Cancer Cells ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Human Lung Cancer Cells ◽

Intracellular Ca

Download Full-text

Ciprofloxacin Enhances TRAIL-Induced Apoptosis in Lung Cancer Cells by Upregulating the Expression and Protein Stability of Death Receptors through CHOP Expression

International Journal of Molecular Sciences ◽

10.3390/ijms19103187 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3187 ◽

Cited By ~ 8

Author(s):

Eun Lim ◽

Yu Yoon ◽

Jeonghoon Heo ◽

Tae Lee ◽

Young-Ho Kim

Keyword(s):

Lung Cancer ◽

Protein Stability ◽

Cancer Cells ◽

Death Receptor ◽

Proteolytic Processing ◽

Receptor Expression ◽

Host Cells ◽

Lung Cancer Cells ◽

Regulation Of Transcription ◽

Induced Apoptosis

Ciprofloxacin (CIP) is a potent antimicrobial agent with multiple effects on host cells and tissues. Previous studies have highlighted their proapoptotic effect on human cancer cells. The current study showed that subtoxic doses of CIP effectively sensitized multiple cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Although TRAIL alone mediated the partial proteolytic processing of procaspase-3 in lung cancer cells, co-treatment with CIP and TRAIL efficiently restored the complete activation of caspases. We found that treatment of lung cancer with CIP significantly upregulated the expression and protein stability of death receptor (DR) 5. These effects were mediated through the regulation of transcription factor CCAT enhancer-binding protein homologous protein (CHOP) since the silencing of these signaling molecules abrogated the effect of CIP. Taken together, these results indicated that the upregulation of death receptor expression and protein stability by CIP contributed to the restoration of TRAIL-sensitivity in lung cancer cells.

Download Full-text