Title: Autophagy-mediated degradation of IAPs and c-FLIPL potentiates apoptosis induced by combination of TRAIL and Chal-24

Journal Article · · Journal of Cellular Biochemistry
DOI: https://doi.org/10.1002/jcb.25397 · OSTI ID:1345225
 [1];  [2];  [3];  [3];  [2];  [4];  [4];  [5];  [5];  [6];  [7];  [6];  [2]
  1. Lovelace Respiratory Research Institute, Albuquerque, NM (United States); Office of Scientific and Technical Information (OSTI)
  2. Lovelace Respiratory Research Institute, Albuquerque, NM (United States)
  3. Lovelace Respiratory Research Institute, Albuquerque, NM (United States); Sichuan Univ., Chengdu (People's Republic of China)
  4. Chongqing Medical University, Chongqing (People's Republic of China)
  5. Sichuan Univ., Chengdu (People's Republic of China); Univ. of New Mexico and New Mexico VA Health Care System, Albuquerque, NM (United States)
  6. Sichuan Univ., Chengdu (People's Republic of China)
  7. Univ. of Minnesota, Minneapolis, MN (United States)
+ Show Author Affiliations

Combination chemotherapy is an effective strategy for increasing anticancer efficacy, reducing side effects and alleviating drug resistance. In this paper, we report that combination of the recently identified novel chalcone derivative, chalcone-24 (Chal-24), and TNF-related apoptosis-inducing ligand (TRAIL) significantly increases cytotoxicity in lung cancer cells. Chal-24 treatment significantly enhanced TRAIL-induced activation of caspase-8 and caspase-3, and the cytotoxicity induced by combination of these agents was effectively suppressed by the pan-caspase inhibitor z-VAD-fmk. Chal-24 and TRAIL combination suppressed expression of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein large (c-FLIPL) and cellular inhibitor of apoptosis proteins (c-IAPs), and ectopic expression of c-FLIPL and c-IAPs inhibited the potentiated cytotoxicity. In addition, TRAIL and Chal-24 cooperatively activated autophagy. Suppression of autophagy effectively attenuated cytotoxicity induced by Chal-24 and TRAIL combination, which was associated with attenuation of c-FLIPL and c-IAPs degradation. In conclusion, these results suggest that Chal-24 potentiates the anticancer activity of TRAIL through autophagy-mediated degradation of c-FLIPL and c-IAPs, and that combination of Chal-24 and TRAIL could be an effective approach in improving chemotherapy efficacy.

Research Organization:
Lovelace Respiratory Research Inst., Albuquerque, NM (United States)
Sponsoring Organization:
USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Grant/Contract Number:
SC0001173; SC0004079
OSTI ID:
1345225
Journal Information:
Journal of Cellular Biochemistry, Journal Name: Journal of Cellular Biochemistry Journal Issue: 5 Vol. 117; ISSN 0730-2312
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (7)

Chloroquine augments TRAIL-induced apoptosis and induces G2/M phase arrest in human pancreatic cancer cells journal March 2018
Cordycepin induces autophagy-mediated c-FLIPL degradation and leads to apoptosis in human non-small cell lung cancer cells journal December 2016
Ophiopogonin B sensitizes TRAIL-induced apoptosis through activation of autophagy flux and downregulates cellular FLICE-like inhibitory protein journal December 2017
Down-regulation of intracellular anti-apoptotic proteins, particularly c-FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL journal May 2018
Autophagy as a mechanism of Apo2L/TRAIL resistance journal August 2018
Cigarette smoke exposure enhances transforming acidic coiled-coil–containing protein 2 turnover and thereby promotes emphysema journal January 2020
Chloroquine augments TRAIL-induced apoptosis and induces G2/M phase arrest in human pancreatic cancer cells journal March 2018

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHAL-24
TRAIL
apoptosis
autophagy
c-FLIP
c-IAP