Table 1.

Interference of anti-cancer agents with different mechanisms of calcium homeostasis. This table illustrates which calcium mediating processes are involved, the actual concentrations (doses) needed, the experimental model, and whether apoptosis or proliferations are involved.

Drug Class	Drugs	Axis/Mechanism of Induction of Cell Death	Concentration Range	Apoptosis	Proliferation	Cell Line	References
Platinum agents (cytotoxic alkylating agent)	Cisplatin	[Ca2+]i ↑↑ by influx of extra cellular calcium. [Ca2+]i ↑↑ / ER stress / mitochondrial Ca2+ over load / caspase 3 activation.	1 µM 5 µg/ml	↑↑	↓↓	MCF-7 SH-SY5Y HeLa-S3	[31,71,72,73]
Anti-metabolites	5-Fluorouracil	Ca2+-CaM-p53 activation, Ca2+ influx partially through L-type Ca2+ channel. Ca2+ entry through TRPV1 / mitochondrial ROS production / caspase 8.	768 μM, 25 μM	↑↑	↓↓	HCT116 MCF-7	[74,75]
Inorganic arsenic compounds	As2O3	IP3R, RyR / [Ca2+]i ↑↑ / DNA damage / caspase 3. ↑↑ER–mitochondrial Ca2+ transfer. ↓↓ ERK1 and ERK2	1 µM	↑↑	↓↓	SH-SY5Y Pml-/- mice NB4 cells U937	[31,76,77,78]
Anthracyclines	Doxorubicin	[Ca2+]i modulation - ERK1/2 inactivation, activation of pro apoptotic BIM pathway and mitochondrial Ca2+ overload.	500 nM–1 µM	↑↑	↓↓	MDA-MB-231	[79]
Taxanes	Paclitaxel Docetaxel	In activation of PMCA2/calcineurin A and activation of calcineurin A /NFAT pathway/ ↑↑ pro-apoptotic protein Fas ligand. External calcium influx, inhibition of bcl2/ IP3R-ER-[Ca2+]i.	1 nM 10-6 M	↑↑		MDA-MB-231 MCF-7 MDA-MB-468	[80,81]
Natural compounds	Chalcones Quercetin EGCG Piceatannol Etoposide; (semi-synthetic) Resveratrol Curcumin Saikosaponin-d	Ca 2+ / ER stress / caspase 12. G-protein / IP3R-ER-[Ca2+]i, / modulation of p53 / transcription of pro-apoptotic genes. SERCA↓↓ activity / [Ca2+]i ↑↑ / increased mitochondrial Ca2+ uptake. SERCA ↓↓ / [Ca2+]i ↑↑ / ER stress / Autophagy mediated cell death.	30–40 µM 50–100 µM 10 µM	↑↑		L1210 MDA-MB-231 MYCN2 HeLa SW480 (colon) MCF-7	[55,82,83,84,85,86]
Camptothecin analog	Topotecan	Increased [Ca2+]i, altered expression of calcium regulating proteins.	0.01 µM	↑↑	↓↓	SH-SY5Y	[87]
Hormonal receptor modulator	Tamoxifen	[Ca2+]i ↑↑ by influx of extra cellular calcium and release of Ca2+ from multiple stores. VGCC	5–10 µM	↑↑		MCF-7 MG63 ZR-75-1 SCC BFTC	[88,89,90,91,92]
DNA methylation and HDAC modulators	TSA Azacitidine Digitoxin Pyrithion zinc Disulfiram	↑↑SERCA3 / apoptosis. SOC / [Ca2+]i ↑↑ / CamK / via MeCP2 / reactivation of tumor suppressor genes.	50 nM–5 µM	↑↑		KATO-III (gastric carcinoma) YB5 (colon)	[93,94]