Azorella compacta methanolic extract induces apoptosis via activation of mitogen-activated protein kinase

Abstract

Azorella compacta Phil. (AC) is an alpine medicinal plant used traditionally for antibacterial treatment. Recent studies have revealed that this plant also has anti‑diabetic effects, but that it is toxic. The present study investigated the underlying mechanisms of action of AC extract against human leukemia HL60 cells. Apoptosis induction was measured by MTT assay, fluorescence microscopy, DNA fragmentation assay, flow cytometric analysis, reverse transcription quantitative polymerase chain reaction and western blot analyses. It was found that AC extract inhibited the growth of HL60 and other cancer cell lines in a dose‑dependent manner. The cytotoxic effects of AC extract on HL60 cells were associated with apoptosis characterized by DNA fragmentation and dose‑dependent increases in Annexin V‑positive cells, as determined by flow cytometric analysis. AC‑extract‑induced apoptosis was accompanied by activated/cleaved caspase‑3, caspase‑9 and poly(adenosine diphosphate‑ribose) polymerase (PARP). The increases in apoptosis were also associated with decreases of the apoptosis-inhibitor B-cell lymphoma 2 (Bcl‑2), upregulation of pro‑apoptotic Bcl-2-associated X (Bax) protein and downregulation of anti‑apoptotic Bcl extra large protein. Furthermore, western blot analysis of mitogen-activated protein kinase (MAPK)-associated proteins indicated that treatment with AC extract increased the levels of c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38. In addition, the expression of Bax and cleaved PARP was blocked when AC treatment was performed in the presence of MAPK inhibitors. It was therefore concluded that AC induced apoptosis in human leukemia HL60 cells via an intrinsic pathway controlled through MAPK-associated signaling.

Anticancer properties of Tulbaghia violacea regulate the expression of p53-dependent mechanisms in cancer cell lines

“…Similarly, p53 was significantly increased in HeLa and ME-180 cells at both the protein and gene levels. p53 upregulation, as further supported by the increase in Bak and Bax in both cervical cancer cell lines with ATM and Puma, occurred in cancer cells treated with both methanol extract and hexane extract [20][21][22][23][24][25] . These results support the earlier observed MTT and cell morphology results and further indicate that apoptosis is caused by plant extract-induced activation of p53.…”

Future in the Past: Azorella glabra Wedd. as a Source of New Natural Compounds with Antiproliferative and Cytotoxic Activity on Multiple Myeloma Cells

“…Our data agree with previous studies that described the cytotoxic activity on solid and haematological malignancies of other Azorella extracts. Sung et al reported the cytotoxic activity of methanolic extract of A. compacta and its ability to induce apoptosis on leukemic HL60 cells [ 34 ]. Previously, another work described the antiproliferative activity of a new chalcone from Azorella madreporica on colon, breast, and prostate cancer cells [ 56 ].…”

“…Another essential characteristic of an antitumor drug is the ability to induce tumor cell apoptosis. In fact, the simultaneous ability of a substance to inhibit cell growth and to induce apoptosis allows discrimination between anti-tumor agents and toxic ones [ 34 ]. Our data showed a significant increase of apoptotic cells during treatment with the AG CHCl 3 fraction.…”

“…Kabeel et al (2018) showed the anti-leukemic effects of a mixture of four water plant extracts ( Arctium lappa , Ulmus rubra , Rumex acetosella , and Rheum palmatum ) in a leukemic rat model [ 33 ]. In addition, it was previously reported that Azorella compacta methanolic extract induced apoptosis in leukemia cells [ 34 ].…”

Advances in Azorella glabra Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization

“…Plants of Azorella genus are commonly used as infuse in folk medicine in the Andean region of South America to treat a variety of ailments, such as colds, asthma, bronchitis and different conditions in which the main symptoms include inflammation and pain [ 14 , 15 , 16 ]. Although the antiproliferative and proapoptotic effects of Azorella genus have been proven in various tumors, including hematologic malignancies [ 14 , 17 ], little information is available for Azorella glabra (AG) Wedd., an endemic Bolivian species also known as Azorella diapensioides A. Gray and popularly called “ yareta ” [ 18 ].…”