Cell and Cancer Type | Inducer of Ca2+ Imbalance and Autophagy | Ca2+ Modulation and Consequences to Autophagy | Autophagy Modulationa | Role in Autophagy | Reference |
---|---|---|---|---|---|
MCF7 breast cancer | Extracellular ATP (release of Ca2+ from the ER through IP3-R) | BAPTA/AM: reduces the % of GFP-LC3+ cells from 40% to 5% | 3-MA (35% to < 5%) | Not assessed | Høyer-Hansen et al., 2007 |
BECN1 KD (35% to 5%) | |||||
ATG7 KD (35% to 12%) | |||||
MCF7 breast cancer | Ionomycin (Ca2+ ionophore) | BAPTA/AM: reduces the % of GFP-LC3+ cells from 40% to 10% | 3-MA (35% to < 5%) | Not assessed | Høyer-Hansen et al., 2007 |
BECN1 KD (35% to 15%) | |||||
ATG7 KD (35% to 12%) | |||||
MCF7 breast cancer | Thapsigargin (TG; inhibitor of ER Ca2+- ATPase which maintains high levels of Ca2+ in the cytosol) | BAPTA/AM: reduces the % of GFP-LC3+ cells from 52% to 5% | 3-MA (45% to 18%) | No assessed | Høyer-Hansen et al., 2007 |
BECN1 KD (45% to 30%) | |||||
ATG7 KD (45% to 28%) | |||||
MCF7 breast cancer | Vitamin D analog EB1089 (increases cytosolic Ca2+, but the mechanism is not fully known) | Not assessed | 3-MA (80% to 20%) - decreased cell death | Cytotoxic | Høyer-Hansen et al., 2005 |
Overexpression of BECN1 increased cell death | |||||
Hela cervix adenocarcinoma | Starvation using HBSS (increases cytosolic Ca2+ from the ER by IP3-R; also disrupts the IP3-R/Bcl-2/BECN1 complex) | BAPTA/AM and xestospongin (IP3-R inhibitor): reduces the % of GFP-LC3-positive cells and the LC3II levels to control levels | Not assessed | Not assessed | Decuypere, 2011 |
Hela cervix adenocarcinoma | Starvation using HBSS (increases cytosolic Ca2+ from the ER by IP3-R; also disrupts the IP3-R/Bcl-2/BECN1 complex) | Overexpression of Bcl2: reduced around a half the percentage of GFP-LC3-positive cells | Not assessed | Not assessedb | Vicencio, 2009 |
HCT116 colon cancer | ATP; | Not assessed | ATG6 KD and ATG8 KD - increased caspase activation and apoptotic cell death from ∼30% to 47% and 62% respectively; | Cytoprotective | Ding, 2007 |
TG-induced ER stress | 3MA also increased cell death, but data are not shown | ||||
A23187-induced ER stress (Ca2+ ionophore) | |||||
DU145 prostate cancer | ATP | Not assessed | ATG6 KD, ATG8 KD and 3-MA induced cell death, but data are not shown. | Cytoprotective | Ding, 2007 |
TG-induced ER stress; | Obs: the efficiency is not shown | ||||
A23187-induced ER stress (Ca2+ ionophore) | |||||
Murine embryonic fibroblasts | TG-induced ER stress | Not assessed | ATG5 KD decreased cell death | Cytotoxic | Ding, 2007 |
A23187-induced ER stress | |||||
CCD-18Co normal colon | TG-induced ER stress | Not assessed | 3-MA decreased cell death | Cytotoxic | Ding, 2007 |
A23187-induced ER stress | |||||
HepG2 Hepatocarcinoma | TG-induced ER stress | Not assessed | Rapamycin and metyrapone (mTOR inhibitor): increased autophagy and cell viability | Cytoprotective (indirect) | Kapuy, 2014 |
DT40 chicken lymphoma | IP3-R triple knockout (TKO) cells | Restoration of IP3-R expression decreased basal autophagy | Rapamycin: increased autophagy in WT but not in DT40 TKO cells | Not assessed b | Khan and Joseph, 2010 |
ER, endoplasmic reticulum; IP3-R, inositol 1,4,5-triphosphate receptor.
KD, knockdown; TG, thapsigargin; 3-MA, 3-methyladenin.
↵a The percentages in the parentheses indicate the percentage of autophagy-positive cells before (first value) and after (second value) autophagy inhibition.
↵b Despite not being assessed, in these contexts, autophagy is known to be cytoprotective (Lum et al., 2005; Onodera and Ohsumi, 2005).