Abstract
Dual-hit metabolic modulator LDCA synergistically potentiates doxorubicin to counter melanoma progression.
Highlights
Doxorubicin is extensively used in chemotherapeutic regimens; its efficacy is poor in the treatment of human melanoma, the combination of doxorubicin with other chemotherapeutic agents has been signi cantly effective.[36]
LDCA is a dual-hit metabolic modulator that inhibits LDH-A enzyme activity to stimulate apoptosis in the malignant population; to exploit the mechanism of relieving toxicity, we assessed the effect of LDCA in combination with doxorubicin in mitigating cancer
The results show that 500 nM of doxorubicin treatment affected $40% melanoma viability, whereas treatment with 25 mM of LDCA alone arrested $50% cell growth a er 72 h, demonstrating a dose-dependent cytotoxic effect against the cancerous population (Fig. 1A–C)
Summary
Most of the common human cancers are malignant neoplasms of the skin, and despite signi cant efforts, they remain poorly understood at the molecular level and fail to respond to conventional chemotherapy.[1,2,3,4] patients harboring this recurrent disease highlight the unmet need and importance of new anticancer agents that would replace and/or supplement the therapeutic options available currently.[4]. Cells were treated with 500 nM doxorubicin, 20 mM LDCA, and their combination for 24 h and harvested, resuspended in 400 ml of binding buffer, and incubated with Annexin-V FITC and PI for estimating apoptosis. Cells were cultured on coverslips overnight, treated with 500 nM doxorubicin, 20 mM LDCA, either alone or in combination for 16 h at 37 C, washed with PBS, and incubated with 10 mg mlÀ1 of JC-1 at 37 C for 15 min. Cells were seeded on coverslips, incubated at 37 C with 5% CO2, and treated with a combination of 500 nM doxorubicin and 20 mM LDCA for 16 h. All experiments were performed in accordance with the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India, and as recommended by the animal ethics committee of CSIR-Indian Institute of Chemical Biology
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