Nimbolide from Neem (Azadirachta indica) Inhibits Pancreatic Cancer Growth and Metastasis

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Neem, also known as Nimtree or Indian Lilac is known by its botanical name, Azadirachta indica, and is a tree in the mahogany family Meliaceae.  It is one of two species in the genus Azadirachta, and is native to India and the Indian subcontinent including Nepal, Pakistan, Bangladesh and Sri Lanka.

Neem-Tree

Neem tree

Neem (नीम) is a Hindi noun derived from Sanskrit Nimba (निंब).

Neem leaves and Neem leaf products have been traditionally used in Ayurvedic medicine for centuries.  Ayurevedic practitioners have used Neem leaves and the oil for a number of conditions and believe it to be:  1

  • antihelmenthic
  • antifungal
  • antidiabetic
  • antibacterial
  • antiviral

Researchers have identified more than 135 compounds from different parts of Neem, primarily from the leaves and seeds.  A short list of the chemical constituents of Neem are as follows:  2

  • isoprenoids
  • protomeliacins
  • limonoids
  • azadirone
  • secomeliacins
  • nimbin
  • salanin
  • azadirachtin
  • isomeldenin
  • nimbin
  • nimbinene
  • 6-desacetyllnimbinene
  • nimbandiol, immobile
  • nimocinol
  • quercetin
  • beta-sitosterol
  • zafaral [24,25,26,27-tetranorapotirucalla-(apoeupha)-6alpha-methoxy-7alpha-acetoxy-1,14-dien-3,16-dione-21-al]
  • meliacinanhydride [24,25,26,27-tetranorapotirucalla-(apoeupha)-6alpha-hydroxy,11alpha-methoxy-7alpha,12alpha-diacetoxy,1,14,20(22)-trien-3-one]

One very important tetranortriterpenoid limonoid isolated from the leaves and flowers of Neem is Nimbolide.  3  This limonoid has been shown to possess numerous biological activities such as:

  • antifeedant  4
  • antimalarial  5 
  • antimicrobial  6 
  • anticancer   7  8  9  10  11 

Nimbolide exhibits antiproliferative activity in a wide variety of tumor cells, including:

  • neuroblastoma
  • osteosarcoma
  • choriocarcinoma  12 
  • cervical cancer  13 
  • leukemia
  • melanoma  14
  • colorectal cancer  15 

Chemoprevention is a strategy by using medicines to treat a precancerous condition or to keep cancer from starting and to reverse or retard the multistep process of carcinogenesis.

Nimbolide is such a potenetial natural medicine used for chemoprevention since it exhibits multiple pharmacological effects by inhibiting tumorigenesis and metastasis without any toxicity and unwanted side effects.

Nimbolide exhibits anticancer activity through selective modulation of multiple cell signaling pathways linked to:  16

  • inflammation
  • survival
  • growth
  • invasion
  • angiogenesis
  • metastasis

A study published 25 January 2016 in Nature.com Scientifc Reports entitled “Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition”, assessed the anticancer properties of nimbolide against pancreatic cancer.

The researchers stated:

“Our data reveal that nimbolide induces excessive generation of reactive oxygen species (ROS), thereby regulating both apoptosis and autophagy in pancreatic cancer cells. Experiments with the autophagy inhibitors 3-methyladenine and chloroquine diphosphate salt and the apoptosis inhibitor z-VAD-fmk demonstrated that nimbolide-mediated ROS generation inhibited proliferation (through reduced PI3K/AKT/mTOR and ERK signaling) and metastasis (through decreased EMT, invasion, migration and colony forming abilities) via mitochondrial-mediated apoptotic cell death but not via autophagy. In vivo experiments also demonstrated that nimbolide was effective in inhibiting pancreatic cancer growth and metastasis. Overall, our data suggest that nimbolide can serve as a potential chemo–therapeutic agent for pancreatic cancer.”  17

An area of further research is the complex interplay between apoptosis and autophagy resulting from the nimbolide-induced boost in ROS.  In this study, the anti-cancer effect of nimbolide seems to be via apoptosis, and not via autophagy, which other studies suggest may actually increase cancer cell survival.


Resources:

Organic India – Neem

TheraNeem Organix Neem Leaf

Himalaya Herbal Healthcare Neem


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