Coralyne, a protoberberine alkaloid, causes robust photosenstization of cancer cells through ATR-p38 MAPK-BAX and JAK2-STAT1-BAX pathways

Chemico-biological Interactions
Rahul BhattacharyyaSubrata Chattopadhyay

Abstract

Photodynamic therapy (PDT) provides an effective cancer treatment option but it requires sufficient cellular oxygen concentration to exert its photosensitizing effects. Due to hypoxic nature of most tumors, widespread clinical application of PDT is restricted and warrants development of photosensitizers which can kill cancer cells in ROS independent manner. Previously, we reported significant enhancement of the anti-cancer property of coralyne in presence of ultraviolet-A (UVA) light exposure against several human carcinoma cell lines. This study aimed at unravelling molecular cascades of events in CUVA treatment (coralyne and UVA light)-mediated photosensitization of human skin cancer. The CUVA-treatment caused robust apoptosis of A431 cancer cells, primarily through mitochondrial and lysosomal dysfunctions. Silencing of BAX conferred a significant protection against CUVA-induced apoptosis. Both lysosomal proteases and caspase-8 activation contributed to BID cleavage. Further, our results revealed that a dual signaling axis e.g., ATR-p38 MAPK and JAK2-STAT1 pathways functioned upstream of BAX activation in apoptosis response. Moreover, transient silencing of ATR and pharmacological inhibition of p38-MAPK or JAK2 significantly ...Continue Reading

Citations

Mar 16, 2019·Beilstein Journal of Organic Chemistry·Seema V KanojiaDibakar Goswami
Sep 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kasipandi MuniyandiHeidi Abrahamse
Aug 28, 2020·World Journal of Stem Cells·Zi-Jian ZhangYu Wen

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