Key result
Low doses of bufalin and cinobufotalin combined with hyperthermia or radiation significantly decreased cell viability to 15-40% and increased apoptosis in human lymphoma U937 cells.
Why the study?
Does the combination of low-dose bufadienolides with hyperthermia or radiation increase cytotoxicity in human lymphoma U937 cells?
Does the combination of low-dose bufadienolides with hyperthermia or radiation increase cytotoxicity in human lymphoma U937 cells?
p-value: p=<0.01
Combining low-dose bufadienolides with hyperthermia or radiation enhances cytotoxicity in lymphoma cells, potentially allowing for lower drug doses and reduced cardiotoxicity.
May enhance cytotoxicity at low doses with hyperthermia or radiation; hypothesis-generating and should not yet change practice.
Bufadienolides are constituents of the traditional Chinese medicine Chan Su and are found in toad venom. Cardiovascular side-effects are one of the limiting factors towards developing bufadienolides as chemotherapeutic agents. Thus, in the present study, low doses of bufalin and cinobufotalin, prominent members of the bufadienolides, were investigated for their cytotoxic activity in combination with hyperthermia (HT) or radiation (Rad) therapy. In addition, the underlying mechanism involved was investigated. A DNA fragmentation assay, viability assay and microscopic observation were primarily used to assess the effect of low doses of the two drugs in human lymphoma U937 cells. Furthermore, the effects of these drugs on the mitochondrial membrane potential (MMP) and apoptotic-associated protein activation were investigated. HT/bufadienolide- and RT/bufadienolide-treated samples significantly increased the DNA fragmentation percentile and decreased the MMP, as well as increasing the apoptotic features observed microscopically within a relatively short time (6 h) after treatment. The two combinations affected the expression of important apoptotic markers, including caspase-3 and BH3 interacting domain death agonist. The findings of the current study confirm the additive effect of HT with this group of drugs, directing a novel therapeutic avenue for the clinical use of bufadienolides at lower doses with more restrained cardio toxic side-effects.
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Emam et al. (2017) studied Human lymphoma. Bufalin and cinobufotalin combined with hyperthermia or radiation vs. Single-drug treatment or untreated control was evaluated on Cell viability (p=<0.01). Low doses of bufalin and cinobufotalin combined with hyperthermia or radiation significantly decreased cell viability to 15-40% and increased apoptosis in human lymphoma U937 cells.
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