Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells

Abstract

BackgroundDrug combination therapy to treat cancer is a strategic approach to increase successful treatment rate. Optimizing combination regimens is vital to increase therapeutic efficacy with minimal side effects.Materials and methodsIn the present study, we evaluated the in vitro cytotoxicity of double and triple combinations consisting of 1′S-1′-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP) and cisplatin (CDDP) against 14 various human cancer cell lines to address the need for more effective therapy. Our data show synergistic effects in MCF-7 cells treated with MIP:ACA, MIP:CDDP and MIP:ACA:CDDP combinations. The type of interaction between MIP, ACA and CDDP was evaluated based on combination index being <0.8 for synergistic effect. Identifying the mechanism of cell death based on previous studies involved intrinsic apoptosis and nuclear factor kappa B (NF-κB) and tested in Western blot analysis. Inactivation of NF-κB was confirmed by p65 and IκBα, while intrinsic apoptosis pathway activation was confirmed by caspase-9 and Apaf-1 expression.ResultsAll combinations confirmed intrinsic apoptosis activation and NF-κB inactivation.ConclusionDouble and triple combination regimens that target induction of the same death mechanism with reduced dosage of each drug could potentially be clinically beneficial in reducing dose-related toxicities.

Anti-Cancer Effects of Synergistic Drug–Bacterium Combinations on Induced Breast Cancer in BALB/c Mice

“…Meanwhile, initial metastasis biomarkers, such as VEGF and MMP-9, revealed that combination treatments of MIP, ACA, and CDDP against highly metastatic tumor models successfully downregulated these protein levels. Also, as previously described, ACA, MIP, and CDDP in combination was also shown to enhance apoptosis cell death via intrinsic and extrinsic means and reduce problems related to drug dosage [20]. Additionally, the upregulation of cell cycle-regulated p300 and p21 was also observed.…”

“…Optimized ACA, CDDP [7,14], and MIP [8] standalone treatment doses were obtained from previous in vivo studies, which showed that these doses are safe to be used. For double and combination studies, the quarter maximal inhibitory concentration (IC 25 ) values were used since these doses were shown to have synergistic interactions in the in vitro analysis [20].…”

2‐(6‐Hydroxyhexylthio)‐5,8‐dimethoxy‐1,4‐naphthoquinone Induces Apoptosis through ROS‐Mediated MAPK, STAT3, and NF‐κB Signalling Pathways in Lung Cancer A549 Cells

“…Some studies suggested that celecoxib induced apoptosis and cell cycle arrest via inhibition of STAT3 phosphorylation in NPC cells [ 33 , 34 ]. The NF- κ B signalling pathway is associated with the growth and survival of cancer cells [ 35 ]. I κ B- α is an important factor in the NF- κ B family of inhibitors, whose phosphorylation is closely related to NF- κ B activation.…”

Network Pharmacology-Based Study to Uncover Potential Pharmacological Mechanisms of Korean Thistle (Cirsium japonicum var. maackii (Maxim.) Matsum.) Flower against Cancer

“…Current anti-inflammatory agents for cancer treatment NSAIDs, including Cox-2, due to fewer adverse effects and a lower mortality rate [ 7 ]. Most commonly, anti-cancer agents aim to inhibit DNA replication and induce cancer cell death; however, cancer chemotherapeutics also attack healthy cells resulting in serious side effects such as nausea, vomiting, hair loss, and fatigue [ 8 , 9 , 10 ]. On the other hand, traditional herbal plants with innovative bioactives and secondary metabolites play an essential role as effective anti-inflammatory, anti-oxidant, or anti-cancer agents [ 11 ].…”