TY - JOUR
T1 - A novel thienopyrimidine analog, tph104, mediates immunogenic cell death in triple-negative breast cancer cells
AU - Tukaramrao, Diwakar Bastihalli
AU - Malla, Saloni
AU - Saraiya, Siddharth
AU - Hanely, Ross Allen
AU - Ray, Aniruddha
AU - Kumari, Shikha
AU - Raman, Dayanidhi
AU - Tiwari, Amit K.
N1 - Publisher Copyright:
© 2021 by the authors. Li-censee MDPI, Basel, Switzerland.
PY - 2021/4/2
Y1 - 2021/4/2
N2 - Enhancing the tumor immunogenic microenvironment has been suggested to circumvent triple-negative breast cancer (TNBC) resistance and increase the efficacy of conventional chemo-therapy. Here, we report a novel chemotherapeutic compound, TPH104, which induces immuno-genic cell death in the TNBC cell line MDA-MB-231, by increasing the stimulatory capacity of dendritic cells (DCs), with an IC50 value of 140 nM. TPH104 (5 µM) significantly increased ATP levels in the supernatant and mobilized intracellular calreticulin to the plasma membrane in MDA-MB-231 cells, compared to cells incubated with the vehicle. Incubating MDA-MB-231 cells for 12 h with TPH104 (1–5 µM) significantly increased TNFα mRNA levels. The supernatants of dying MDAMB-231 cells incubated with TPH104 increased mouse bone marrow-derived DC maturation, the expression of MHCII and CD86 and the mRNA expression of TNFα, IL6 and IL12. Overall, these re-sults indicate that TPH104 induces immunogenic cell death in TNBC cells, in part, by activating DCs.
AB - Enhancing the tumor immunogenic microenvironment has been suggested to circumvent triple-negative breast cancer (TNBC) resistance and increase the efficacy of conventional chemo-therapy. Here, we report a novel chemotherapeutic compound, TPH104, which induces immuno-genic cell death in the TNBC cell line MDA-MB-231, by increasing the stimulatory capacity of dendritic cells (DCs), with an IC50 value of 140 nM. TPH104 (5 µM) significantly increased ATP levels in the supernatant and mobilized intracellular calreticulin to the plasma membrane in MDA-MB-231 cells, compared to cells incubated with the vehicle. Incubating MDA-MB-231 cells for 12 h with TPH104 (1–5 µM) significantly increased TNFα mRNA levels. The supernatants of dying MDAMB-231 cells incubated with TPH104 increased mouse bone marrow-derived DC maturation, the expression of MHCII and CD86 and the mRNA expression of TNFα, IL6 and IL12. Overall, these re-sults indicate that TPH104 induces immunogenic cell death in TNBC cells, in part, by activating DCs.
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U2 - 10.3390/cancers13081954
DO - 10.3390/cancers13081954
M3 - Article
AN - SCOPUS:85104358122
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 8
M1 - 1954
ER -