Nimbolide epigenetically regulates autophagy and apoptosis in breast cancer

Toxicology in Vitro : an International Journal Published in Association with BIBRA
Venkatesh PooladandaChandraiah Godugu

Abstract

Autophagy is a critical regulator of cellular homeostasis and its dysregulation often results in various disease manifestations, including cancer. Nimbolide, an active chemical constituent of neem (Azadirachta indica) exhibits potent anticancer effects. Although, nimbolide mediated apoptosis activation in breast cancer cells is well known. Nevertheless, its role in autophagy induction mechanism and epigenetic alteration is not explored previously. Our current study intended to bridge the gaps in the existing research by exploring the potential of nimbolide in inducing autophagy, which could counter regulate the transformations in breast cancer. In our studies, nimbolide significantly inhibited the cell proliferation of MDA-MB-231 and MCF-7 cells with IC50 values of 1.97 ± 0.24 and 5.04 ± 0.25 μM, respectively. Nimbolide markedly arrested the cell cycle progression and cell survival with loss of mitochondrial membrane potential by reducing Bcl-2 concomitantly inducing Bax and caspases protein expression with modulation of HDAC-2 and H3K27Ac expression. Consequently, characteristic autophagolysosome accumulation was observed by acridine orange, monodansylcadaverine (MDC) and Lysotracker Red staining. Moreover, nimbolide induced a...Continue Reading

Citations

Jul 4, 2019·Nanomedicine·Amit KhuranaChandraiah Godugu
Jul 30, 2019·Nanomedicine·Shrikant KirwaleChandraiah Godugu
Dec 18, 2019·Journal of Cellular Physiology·Sowjanya ThatikondaChandraiah Godugu
Dec 31, 2019·Journal of Food and Drug Analysis·Yen-Chun KohMin-Hsiung Pan
Mar 3, 2020·Frontiers in Pharmacology·Amit S ChoudhariOm Prakash
Dec 20, 2018·International Journal of Molecular Sciences·Marius Alexandru MogaClaudia Gavriș
Mar 20, 2021·Journal of Medicinal Chemistry·Siddavaram NaginiRajakishore Mishra
Jun 3, 2021·International Journal of Molecular Sciences·Alicja K SurowiakDaniel J Strub
Dec 21, 2019·Chemico-biological Interactions·Amanda Blanque BecceneriMarcia Regina Cominetti
Dec 9, 2020·Journal of Medicinal Chemistry·Yulin Ren, A Douglas Kinghorn
Aug 27, 2021·Journal of Inorganic Biochemistry·Yuanyuan ZhangYunjun Liu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.