PMID- 31784542
OWN - NLM
STAT- MEDLINE
DCOM- 20201113
LR  - 20210203
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Nov 29
TI  - Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses 
      NF-kappaB Activation, Modulates LncRNA Expression and Exhibit Activities Against 
      Breast Cancer.
PG  - 17980
LID - 10.1038/s41598-019-52971-3 [doi]
LID - 17980
AB  - 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-kappaB-p65 nuclear 
      translocation induced by okadaic acid (OA) was suppressed by the sesquiterpene. 
      IDET also suppressed the expression of NF-kappaB 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.
FAU - Verma, Sumit S
AU  - Verma SS
AD  - Laboratory for Translational Cancer Research, Department of Biochemistry, 
      Institute of Science, Banaras Hindu University, Varanasi, 221 005, India.
FAU - Rai, Vipin
AU  - Rai V
AD  - Laboratory for Translational Cancer Research, Department of Biochemistry, 
      Institute of Science, Banaras Hindu University, Varanasi, 221 005, India.
FAU - Awasthee, Nikee
AU  - Awasthee N
AD  - Laboratory for Translational Cancer Research, Department of Biochemistry, 
      Institute of Science, Banaras Hindu University, Varanasi, 221 005, India.
FAU - Dhasmana, Anupam
AU  - Dhasmana A
AD  - Swami Rama Himalayan University, Jolly Grant, Dehradun, 248 016, India.
FAU - Rajalaksmi, Dhanya S
AU  - Rajalaksmi DS
AD  - Division of Organic Chemistry, CSIR-National Institute for Interdisciplinary 
      Science and Technology, Thiruvanantthapuram, India.
FAU - Nair, Mangalam S
AU  - Nair MS
AD  - Division of Organic Chemistry, CSIR-National Institute for Interdisciplinary 
      Science and Technology, Thiruvanantthapuram, India.
FAU - Gupta, Subash C
AU  - Gupta SC
AD  - Laboratory for Translational Cancer Research, Department of Biochemistry, 
      Institute of Science, Banaras Hindu University, Varanasi, 221 005, India. 
      sgupta@bhu.ac.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191129
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Lactones)
RN  - 0 (RELA protein, human)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (deoxyelephantopin)
RN  - 0 (isodeoxyelephantopin)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/chemistry/*pharmacology/therapeutic use
MH  - Asteraceae/chemistry
MH  - Breast Neoplasms/*drug therapy/genetics/pathology
MH  - Cell Proliferation/genetics
MH  - Female
MH  - G2 Phase Cell Cycle Checkpoints/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Lactones/chemistry/*pharmacology/therapeutic use
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - RNA, Long Noncoding/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Sesquiterpenes/chemistry/*pharmacology/therapeutic use
MH  - Signal Transduction/*drug effects/genetics
MH  - Stereoisomerism
MH  - Transcription Factor RelA/metabolism
PMC - PMC6884568
COIS- The authors declare no competing interests.
EDAT- 2019/12/01 06:00
MHDA- 2020/11/18 06:00
PMCR- 2019/11/29
CRDT- 2019/12/01 06:00
PHST- 2019/06/11 00:00 [received]
PHST- 2019/10/24 00:00 [accepted]
PHST- 2019/12/01 06:00 [entrez]
PHST- 2019/12/01 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2019/11/29 00:00 [pmc-release]
AID - 10.1038/s41598-019-52971-3 [pii]
AID - 52971 [pii]
AID - 10.1038/s41598-019-52971-3 [doi]
PST - epublish
SO  - Sci Rep. 2019 Nov 29;9(1):17980. doi: 10.1038/s41598-019-52971-3.