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

Hiroki Doi,Taei Matsui,Atsushi Ogasawara,Hiromu Takematsu,Seiji Imamura,Yuki Higashimoto,Hidehiko Akiyama,Itsuro Katsuda,Tamae Ohye,Johannes M Dijkstra

doi:10.12688/f1000research.53595.2

Hiroki Doi, Taei Matsui + Show 8 more

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https://doi.org/10.12688/f1000research.53595.2

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Journal: F1000Research	Publication Date: Dec 22, 2021
Citations: 1	License type: CC BY 4.0

Affiliation: Fujita Health University

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 dose-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 (thus forming: 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.) 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.

Highlights

Many plant-derived products possess a potential for use in chemotherapy
Effects of Andro on the cell viability The effects of Andro, Andro was compared with cytosine arabinoside (Ara-C), and VCR on the viability of THP-1 and H929 cells were compared by incubating the cells for 24 h with or without an agent at the indicated concentrations, followed by an MTT assay (Figure 1)
They reduced the viability of THP-1 cells to 50-55%, whereas Ara-C only had a slight impact on H929 cells (Figure 1)

Summary

Introduction

Many plant-derived products possess a potential for use in chemotherapy. For example, vincristine (VCR) and vinblastine—two natural alkaloids isolated from Vinca rosea—inhibit cell division and are commonly used in anticancer medicine (Varma et al, 2011). Andro has been shown to have anti-tumor activities against solid and hematopoietic tumor cell lines, established from colon-, gastric-, liver-, breast-, and prostatic cancers, leukemia, and lymphoma (Banerjee et al, 2016; Chen et al, 2012; Cheung et al, 2005; Dai et al, 2017; Khan et al, 2018; Kim et al, 2005; Yang et al, 2010). Conclusions: Andro induces ROS-dependent apoptosis in monocytic version 2 (revision)

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