Piperlongumine: a natural plant-based compound that is selectively cytotoxic to cancer cells

 

Piper_longum D440820

Scientists at the Broad Institute and Massachusetts General Hospital (MGH) have discovered a novel compound that blocks this response to oxidative stress selectively in cancer cells but spares normal cells, with an effectiveness that surpassed a chemotherapy drug currently used to treat breast cancer. Their findings, based on experiments in cell culture and in mice, appear online in Nature on July 13.

The plant-based compound piperlongumine (PL), derived from the fruit of a pepper plant found in southern India and southeast Asia, appears to kill cancer cells by jamming the machinery that dissipates high oxidative stress and the resulting ROS. Normal cells have low levels of ROS, in tune with their more modest metabolism, so they don’t need high levels of the anti-oxidant enzymes that PL stymies once they pass a certain threshold.

Taking out a cancer’s co-dependency:
Novel compound selectively kills cancer cells by blocking their response to oxidative stress

Redox-directed cancer therapeutics: Taurolidine and Piperlongumine as broadly effective antineoplastic agents (Review)

Synthesis, cellular evaluation, and mechanism of action of piperlongumine analogs

Selective killing of cancer cells by a small molecule targeting the stress response to ROS

Piperlongumine Induces Apoptosis and Synergizes with Cisplatin or Paclitaxel in Human Ovarian Cancer Cells

Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer

Targeting Aberrant Glutathione Metabolism to Eradicate Human Acute Myelogenous Leukemia Cells

Methyl Jasmonate – a natural anti-cancer compound with several modes of action

Methyl Jasmonate is a plant stress hormone that has significant anti-cancer properties. So how does MJ work? Let me count the ways. It arrests cell cycle, inhibiting cell growth and proliferation; causes cell death through the intrinsic/extrinsic pro-apoptotic, p53-independent apoptotic, and non-apoptotic (necrosis) pathways; detaches hexokinase from the voltage-dependent anion channel, dissociating glycolytic and mitochondrial functions, decreasing the mitochondrial membrane potential, favoring cytochrome c release and ATP depletion, activating pro-apoptotic and inactivating anti-apoptotic proteins; induces reactive oxygen species mediated responses; stimulates MAPK-stress signaling and redifferentiation in leukemia cells; inhibits overexpressed pro-inflammatory enzymes in cancer cells such as aldo-keto reductase 1 and 5-lipoxygenase; inhibits cell migration and shows antiangiogenic and anti-metastatic activities. The complete lack of toxicity to normal cells and the rapidity by which MJ causes damage to cancer cells, turns MJ into a promising anticancer agent that can be used alone or in combination with other agents.

Follow the links for the relevant research:

MJ modes of action

MJ modes of action

Methyl Jasmonate: Putative Mechanisms of Action on Cancer Cells Cycle, Metabolism, and Apoptosis

Jasmonates: Novel Anticancer Agents Acting Directly and Selectively on Human Cancer Cell Mitochondria