Anti-Cancer Agents in Proliferation and Cell Death: The Calcium Connection

Authors

VARGHESE Elizabeth SAMUEL Samson Mathews SADIQ Zuhair KUBATKA Peter LISKOVA Alena BENACKA Jozef PAZINKA Peter KRUŽLIAK Peter BUSSELBERG Dietrich

Year of publication 2019
Type Article in Periodical
Magazine / Source International Journal of Molecular Sciences
MU Faculty or unit

Faculty of Medicine

Citation
Web http://dx.doi.org/10.3390/ijms20123017
Doi http://dx.doi.org/10.3390/ijms20123017
Keywords Intracellular calcium; anti-cancer drugs; apoptosis; proliferation
Description Calcium (Ca2+) signaling and the modulation of intracellular calcium ([Ca2+](i)) levels play critical roles in several key processes that regulate cellular survival, growth, differentiation, metabolism, and death in normal cells. On the other hand, aberrant Ca2+-signaling and loss of [Ca2+](i) homeostasis contributes to tumor initiation proliferation, angiogenesis, and other key processes that support tumor progression in several different cancers. Currently, chemically and functionally distinct drugs are used as chemotherapeutic agents in the treatment and management of cancer among which certain anti-cancer drugs reportedly suppress pro-survival signals and activate pro-apoptotic signaling through modulation of Ca2+-signaling-dependent mechanisms. Most importantly, the modulation of [Ca2+](i) levels via the endoplasmic reticulum-mitochondrial axis and corresponding action of channels and pumps within the plasma membrane play an important role in the survival and death of cancer cells. The endoplasmic reticulum-mitochondrial axis is of prime importance when considering Ca2+-signaling-dependent anti-cancer drug targets. This review discusses how calcium signaling is targeted by anti-cancer drugs and highlights the role of calcium signaling in epigenetic modification and the Warburg effect in tumorigenesis.

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