The Potential Antitumor Effects of Capsaicin

Díaz‐Laviada, Inés; Rodríguez-Henche, Nieves

doi:10.1007/978-3-0348-0828-6_8

Cited by 57 publications

(54 citation statements)

References 113 publications

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“…Capsaicin was reported to bind to the transient receptor potential vanilloid (TRPV1) receptor, leading to desensitization of peripheral nerves to noxious stimuli 11 . Numerous recent research reports have convincingly shown that capsaicin induces cell cycle arrest and apoptotic cancer cell death in a variety of cancer cell lines including colon adenocarcinoma, pancreatic cancer, hepatocellular carcinoma, prostate cancer, breast cancer, and many others 12 . Interestingly, many of the pathways inhibited by capsaicin treatment involve Hsp90 client proteins.…”

Section: Resultsmentioning

confidence: 99%

Progesterone Receptor Chaperone Complex–Based High-Throughput Screening Assay: Identification of Capsaicin as an Inhibitor of the Hsp90 Machine

Patwardhan

Alfa

et al. 2015

SLAS Discovery

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Hsp90 and its co-chaperones are known to be important for cancer cell survival. The N-terminal inhibitors of Hsp90 that are in ongoing clinical trials as anti-tumor agents have unfortunately shown disappointing efficacies in the clinic. Thus, novel inhibitors of the Hsp90 machine with different mechanism of action are urgently needed. We report here the development of a novel high-throughput drug-screening (HTS) assay platform to identify small molecule inhibitors of Hsp90 and its co-chaperones. This assay quantitatively measures the ability of Hsp90 and its co-chaperones to refold/protect the progesterone receptor (PR), a physiological client of Hsp90, in 96-well plate format. We screened the NIH clinical collection drug library and identified capsaicin as a hit molecule. Capsaicin is an FDA-approved drug for topical use in pain management. Cell survival assays showed that capsaicin selectively kills cancer cells and destabilizes several Hsp90 client proteins. Thus, our data may explain the seemingly pleotropic effect of capsaicin.

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Section: Resultsmentioning

confidence: 99%

Progesterone Receptor Chaperone Complex–Based High-Throughput Screening Assay: Identification of Capsaicin as an Inhibitor of the Hsp90 Machine

Patwardhan

Alfa

et al. 2015

SLAS Discovery

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“…Unfortuntely, although tumor cells express higher levels of TRPV1 than normal epithelial cells, they still do not have enough receptors to perform tumor-targeted TRPV1-mediated necrotic-type eradication (Pecze et al, 2016b). Nevertheless, several experiments (Diaz-Laviada and Rodriguez-Henche, 2014) as well as a case report (Jankovic et al, 2010) suggest that vanilloids have anti-cancer activity. The origin of the anticancer effects of vanilloids is not completely solved and it needs further examination.…”

Section: Safety and Efficacy Of Molecular Surgery Agents In Humansmentioning

confidence: 99%

“…The origin of the anticancer effects of vanilloids is not completely solved and it needs further examination. Whether it is TRPV1-mediated or a TRPV1-independent effect is still in question (Diaz-Laviada and Rodriguez-Henche, 2014). To make things more complicated, pain sensing neurons innervate the tumor mass and communicate with the tumors (Li et al, 2013).…”

Section: Safety and Efficacy Of Molecular Surgery Agents In Humansmentioning

confidence: 99%

Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons

2017

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“Molecular neurosurgery” is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target is a specific cell type whose elimination is desired through the molecular surgery procedure. These target cells have the highest innate sensitivity to the molecular surgery agent usually due to the highest receptor density being in their plasma membrane. The interaction between the ligand and its receptor evokes an overactivity of the receptor. If the receptor is a ligand-activated non-selective cation channel, the overactivity of receptor leads to excess Ca2+ and Na+ influx into the cell and finally cell death. One of the best known examples of such an interaction is the effect of ultrapotent vanilloids on TRPV1-expressing pain-sensing neurons. One intrathecal resiniferatoxin (RTX) dose allows for the receptor-mediated removal of TRPV1+ neurons from the peripheral nervous system. The TRPV1 receptor-mediated ion influx induces necrotic processes, but only in pain-sensing neurons, and usually within an hour. Besides that, target-specific apoptotic processes are also induced. Thus, as a nano-surgery scalpel, RTX removes the neurons responsible for generating pain and inflammation from the peripheral nervous system providing an option in clinical management for the treatment of morphine-insensitive pain conditions. In the future, the molecular surgery concept can also be exploited in cancer research for selectively targeting the specific tumor cell.

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“…Accumulated evidence has also demonstrated that capsaicinoid has potential beneficial effect on the human cardiovascular system [14,15,16]. It has also been reported that capsaicinoid possesses antitumor activity [17,18]. Capsaicinoids have been shown to possess antioxidant activity with an ability to prevent excessive formation of ROS (reactive oxygen species) [19,20] There are few reports on the antioxidant activity of capsaicin [21,22].…”

Section: Introductionmentioning

confidence: 99%