Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer

Abstract

The sesquiterpene lactones, Isodeoxyelephantopin (IDET) and Deoxyelephantopin (DET) are known to exhibit activities against some cancer types. The activities of these lactones against breast cancer and the molecular bases is not known. We examined the efficacy of lactones in breast cancer preclinical model. Although both lactones exhibited drug like properties, IDET was relatively effective in comparison to DET. IDET suppressed the proliferation of both invasive and non-invasive breast cancer cell lines. IDET also suppressed the colony formation and migration of breast cancer cells. The assays for Acridine Orange (AO)/Propidium Iodide (PI) staining, cell cycle distribution, phosphatidylserine externalization and DNA laddering suggested the apoptosis inducing potential of IDET. The treatment with IDET also induced an accumulation of cells in the sub-G1 and G2/M phases. The exposure of breast cancer cells to the lactone was associated with a depolarization in mitochondrial membrane potential, and cleavage of caspase and PARP. The lactone induced reactive oxygen species (ROS) generation in breast cancer cells. Further, the use of N-acetyl cysteine (NAC) suppressed IDET induced ROS generation and apoptosis. The NF-κB-p65 nuclear translocation induced by okadaic acid (OA) was suppressed by the sesquiterpene. IDET also suppressed the expression of NF-κB regulated tumorigenic proteins, and induced the expression of proapoptotic gene (Bax) in cancer cells. While the expression of oncogenic lncRNAs was suppressed, the tumor suppressor lncRNAs were induced by the sesquiterpene. Collectively, the modulation of multiple cell signaling molecules by IDET may contribute to its activities in breast cancer cells.

High Expression of COL17A1 Predicts Poor Prognosis and Promotes the Tumor Progression via NF-κB Pathway in Pancreatic Adenocarcinoma

“…Gemcitabine in combination with p65 siRNA can control the proliferation of pancreatic cancer cells and induce apoptosis as well, both in vivo and in vitro, and curtail the growth and angiogenesis of tumors in nude mice, and this can be a welcome solution as pancreatic cancer treatment is an important issue all over the world [ 44 ]. Recently, studies reported that isodeoxyelephantopin (IDET) may function as an anticarcinogenic via the NF- κ B inactivation and the regulation of oncogenic lncRNA expression in breast cancer [ 45 ]. In addition, NF- κ B may present a unique target for tumor avoidance and therapy in combination with inhibition of transcription factors, such as Stat3 [ 46 ].…”

Plant-Derived Natural Biomolecule Picein Attenuates Menadione Induced Oxidative Stress on Neuroblastoma Cell Mitochondria

“…The chemical descriptor and drug-like properties of picein (PubChem ID: 92123) and gastrodin (PubChem ID: 115067) were observed by using Lipinski’s rule of 5 ( ), where this rule was specially designated for the selection of small druggable compounds [ 40 , 41 ]. Conical SMILE IDs is a specific and particular chemical structure characteristic of every chemical compound which is usually mentioned in chemical databases.…”

Deoxyelephantopin and Its Isomer Isodeoxyelephantopin: Anti-Cancer Natural Products with Multiple Modes of Action

“…Elephantopus scaber L., a medicinal plant, is commonly known as “tawmonlar” in Myanmar traditional medicine, “Tutup bumi” in Malaysian, “Elephant’s foot” in English, “Didancao” in traditional Chinese medicines (TCM), and “Gobhi” in Hindi [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Elephantopus genus is widely distributed all over the world, especially in east Asia, southeast Asia, Africa, Australia, India, Europe, and South America [ 16 , 21 , 22 , 23 , 24 , 25 ]. Only Elephantopus scaber, one of the 32 species of genus, is known to grow in India [ 26 , 27 ].…”