Andrographolide, isolated from Andrographis paniculata, induces apoptosis in monocytic leukemia and multiple myeloma cells via augmentation of reactive oxygen species production

Abstract

Background: Andrographolide (Andro) is a diterpenoid component of the plant Andrographis paniculata that is known for its anti-tumor activity against a variety of cancer cells. Methods: We studied the effects of Andro on the viability of the human leukemia monocytic cell line THP-1 and the human multiple myeloma cell line H929. Andro was compared with cytosine arabinoside (Ara-C) and vincristine (VCR), which are well-established therapeutics against hematopoietic tumors. The importance of reactive oxygen species (ROS) production for the toxicity of each agent was investigated by using an inhibitor of ROS production, N-acetyl-L-cysteine (NAC). Results: Andro reduced the viability of THP-1 and H929 in a concentration-dependent manner. H929 viability was highly susceptible to Andro, although only slightly susceptible to Ara-C. The agents Andro, Ara-C, and VCR each induced apoptosis, as shown by cellular shrinkage, DNA fragmentation, and increases in annexin V-binding, caspase-3/7 activity, ROS production, and mitochondrial membrane depolarization. Whereas Ara-C and VCR increased the percentages of cells in the G0/G1 and G2/M phases, respectively, Andro showed little or no detectable effect on cell cycle progression. The apoptotic activities of Andro were largely suppressed by NAC, an inhibitor of ROS production, whereas NAC hardly affected the apoptotic activities of Ara-C and VCR. Conclusions: Andro induces ROS-dependent apoptosis in monocytic leukemia THP-1 and multiple myeloma H929 cells, underlining its potential as a therapeutic agent for treating hematopoietic tumors. The high toxicity for H929 cells, by a mechanism that is different from that of Ara-C and VCR, is encouraging for further studies on the use of Andro against multiple myeloma.

Anti-Cancer Agent: The Labdane Diterpenoid-Andrographolide

“…Treatment with andrographolide at the concentration of 50 µM reduced the viability of the THP-1 (human monocytic leukemia) cell line and NCI-H929 (human IgAkappa-producing multiple myeloma) cell line to 39.2 and 13.0%, respectively, with respect to the untreated cells in a concentration-dependent manner [ 86 ]. The IC 50 values for treating were 31 and 8 µM, for THP-1 and H929 cells, respectively.…”

Andrographolide acts with dexamethasone to inhibit the growth of acute lymphoblastic leukemia CEM‑C1 cells via the regulation of the autophagy‑dependent PI3K/AKT/mTOR signaling pathway

“…Andrographolide (AND) is the major bioactive compound isolated from Andrographis paniculata , a medicinal herb that is widely used in China and other parts of Asia for the treatment of upper respiratory tract infections ( 24 ). It has been found that AND has a wide range of therapeutic actions, including immunosuppressant ( 25 ), antithrombotic ( 26 ), anti-inflammatory ( 27 ), antineoplastic ( 28 ), antiviral ( 29 , 30 ), antibacterial ( 31 ), antidiabetic ( 30 , 32 ), antioxidative ( 33 ), antipyretic ( 34 ), anti-oedematogenic and antinociceptive activities ( 35 ). It has also been reported that AND is a common inhibitor of autophagy ( 36 , 37 ).…”