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Phosphatidylinositol 3‐kinases inhibitor LY 294002 potentiates the cytotoxic effects of doxorubicin, vincristine, and etoposide in a panel of cancer cell lines
Author(s) -
Badinloo Marzieh,
EsmaeiliMahani Saeed
Publication year - 2014
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12043
Subject(s) - doxorubicin , etoposide , apoptosis , cytotoxicity , vincristine , pharmacology , biology , cancer research , cell growth , cytotoxic t cell , cell culture , pi3k/akt/mtor pathway , cancer cell , viability assay , growth inhibition , protein kinase b , cancer , chemotherapy , biochemistry , in vitro , cyclophosphamide , genetics
Many novel therapeutic approaches to overcome chemoresistance have involved targeting specific signaling pathways such as the phosphatidylinositol 3‐kinase ( PI 3K) pathway. PI 3K is a known stress response pathway which is involved in the regulation of cell survival, apoptosis, and growth. Inhibition of this pathway may possibly restore or augment the effectiveness of chemotherapy. Using three human malignant cell lines, we examined the effects of LY 294002 ( PI 3K inhibitor) on chemotherapeutic agent‐induced apoptosis and cytotoxicity. An antimicrotubule agent vincristine, a topoisomerase II inhibitor etoposide, and a DNA cross‐linking agent doxorubicin were used accompanied with LY 294002. Cell viability was determined by MTT assay, and the induction of apoptosis was assessed by immunoblotting of caspase‐3. Blocking the PI 3K/Akt cascade with a PI 3K inhibitor LY 294002 (10 μM) increased the cytotoxic effect of vincristine and doxorubicin on SK ‐ OV ‐3 cell line. Furthermore, LY 294002 showed a greater promoting effect in etoposide‐ and doxorubicin‐induced cytotoxicity on MDA ‐ MB ‐468 and A549 cells. The quantity of cleaved caspase‐3 in cancer cells that had combination therapy was increased compared with that in the cells treated with each drug alone. We suggest that inhibitors of the PI 3K/Akt pathway in combination with chemotherapeutic agents may induce cell death effectively and be a potent modality to treat various types of cancer. The effectiveness of such combination therapy is depending to the used cell line and class of anticancer drug.