Chlorogenic acid induced apoptosis and inhibition of proliferation in human acute promyelocytic leukemia HL-60 cells

Abstract

Chlorogenic acid (CA), is found in high abundance in the leaves of a number of plants and has antibacterial, antiphlogistic, antimutagenic, antioxidant and other biological activities. It reportedly possesses antitumor activity via the induction of apoptosis in chronic myelogenous leukemia (CML) cell lines, including U937 and K562 cells. However, the effects of CA on human acute promyelocytic leukemia (APL) HL‑60 cells remains unknown. In the current study, the ability of CA to cause G0/G1 cycle arrest and induce apoptosis in the treatment of human APL HL‑60 cells was investigated. Following 5 days treatment with 1, 5 and 10 µM CA, cell viability and the effects of CA on the growth of HL‑60 cells were investigated using a growth curve constructed using trypan blue staining. Induction of apoptosis and inhibition of cell proliferation were estimated using Wright's‑Giemsa staining, Hoechst 33342 and propidium iodide (PI) staining, DNA ladder analysis and flow cytometry, following 48 h cell treatment with various doses of CA. The results indicated that the growth of HL‑60 cells reached a plateau phase at 72 h and the proliferation inhibition rate of HL‑60 cells in CA‑treated groups was significantly higher compared with the control, in a time‑ and dose‑dependent manner. However, the level of apoptosis of HL‑60 cells treated with CA markedly increased and formed more apoptotic bodies compared with the cells with no drug treatment, according to the Wright's‑Giemsa staining, Hoechst 33342 and PI staining, respectively. Using DNA ladder analysis and flow cytometry it was shown that a significant characteristic DNA ladder was observed when treated with CA. CA was capable of arresting cell cycle at G0/G1 phase. Apoptosis of HL‑60 cells treated with CA for 48 h was promoted significantly in a dose‑dependent manner, as well as the inhibition of proliferation. The observations revealed that CA inhibits proliferation and induces preprophase apoptosis of HL‑60 cells. Thus, the concentration of 10 µM may be the optimal dose for treatment human acute promyelocytic leukemia.

Chlorogenic acid inhibits hypoxia-induced angiogenesis via down-regulation of the HIF-1α/AKT pathway

“…CGA has been used as a chemoprotective agent for chemotherapy in cancer patients by reducing the cytotoxic effects of anticancer drugs through scavenging reactive oxygen species (ROS) [20]. Also, a direct anti-tumor effect of CGA has been noted in various human cancer cells such as prostate cancer cells [21], acute and chronic myeloid leukemia cells [22,23], lung cancer cells [24], colon cancer cells and liver cancer cells [25]. Furthermore, CGA has been found to decrease urethane-induced lung cancer [26], the growth and progression of prostate cancer xenografts [21] and 12-Otetradecanoylphorbol-13-acetate (TPA) induced epithelial cancer in vivo [27].…”

Cytoprotective effect of chlorogenic acid against hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells through PI3K/Akt-mediated Nrf2/HO-1 signaling pathway

“…Most of studies reported that the pathogenesis of osteoporosis is associated with oxidative stress in osteoblasts [2, 3]. Overproduction of ROS disrupts the balance between oxidation and antioxidant defense systems, leading to bone loss by promoting lipid peroxidation and lowering antioxidant enzymes, inducing apoptosis of osteoblasts and inhibiting bone formation [4–6].…”

“…CGA, a type of polyphenolic compound formed by esterification of caffeic and quinic acids, is the major active ingredient found in many traditional Chinese medicines such as Flos Lonicerae Japonicae and Eucommia Ulmoides , and it is also abundant in some fruits, dietary vegetables, and daily beverages like coffee, pineapple, beans, strawberries and apples [23]. Previous reports have demonstrated that CGA exhibits a wide range of diverse pharmacological effects, including anti-inflammatory, anti-oxidative, and anti-carcinogenic activities [3, 24, 25]. However, the antioxidant effects and molecular mechanisms of CGA in osteoblasts have not been elucidated yet.…”

Chlorogenic Acid Protects against Atherosclerosis in ApoE−/− Mice and Promotes Cholesterol Efflux from RAW264.7 Macrophages

“…Like other dietary polyphenols, CGA has numerous nutritional and pharmacological activities such as antidiabetes [15], antihypertension [16] and antitumor [17]. Importantly, CGA has also been recognized to possess various antiatherosclerotic activities, including hypolipidemic [18], [19], antioxidative [20], [21] and anti-inflammatory [22], [23] properties.…”