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CD147 as potential therapeutic target in AML
treated by ATO and AC-73 used in combination, as com- pared to single agent treatment or control cells (C) (Figure 5D and E).
Altogether, our data demonstrate that AC-73 is a potent, novel anti-proliferative molecule that enhances the sensi- tivity of leukemic cells to conventional chemotherapeutic agents, but also increases ATO-induced autophagy in M3 and non-M3 leukemic cells.
AC-73 increases the sensitivity of primary acute myeloid leukemia blasts co-expressing CD147 and CD371 to chemotherapy
We evaluated the effects of AC-73 used alone and in combination with Ara-C or ATO on primary AML blasts. First, we analyzed CD147 protein expression in samples obtained from different subtypes of AML and we con- trolled the expression of CD34, CD38 and CD371 mark-
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Figure 4. Effects of AC-73 on cell growth, apoptosis and viability of acute myeloid leukemia (AML) cell lines and autophagy. (A) Dose response analysis of AC-73 treatment on leukemic cell growth, as compared to control cells (C). (B) Analysis of the effects of AC-73 treatment performed for 3 days (d3) on leukemic cell apop- tosis, as compared to control leukemic cell (0). Total apoptosis by annexin V/PI (%) detected by using flow cytometric apoptotic assays is indicated. (C and D) Cell via- bility assays on leukemic cells treated: (C) with AC-73 used at different concentrations for 2 days; (D) at different times with 2.5 μM AC-73, as compared to control cells (day 0). (C and D) Viability is presented as percentage viable cell relative to control. (E) Western blot analysis of the autophagy related protein LC3 and its con- version from LC3-I to LC3-II form in leukemic cells treated with AC-73 used at different concentrations, as compared to control (-) cells. (F) Dose response analysis of AC-73 treatment on the autophagy flux in U937 and NB4 leukemic cells, as compared to control cells (0). (G) Induction of autophagy by AC-73 treatment (+) in several AML cell lines, as compared to control cells (-). (A-D, F and G) Mean±Standard Error of Mean is shown. *P<0.05; **P<0.01; ***P<0.001. ns: not significant. (E) One representative western blot experiment out of three is shown. Actin was used as an internal control.
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