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Review
. 2019 Jun 26;24(13):2350.
doi: 10.3390/molecules24132350.

Capsaicin: Effects on the Pathogenesis of Hepatocellular Carcinoma

Cristian Scheau  1 , Ioana Anca Badarau  2 , Constantin Caruntu  3   4 , Gratiela Livia Mihai  1 , Andreea Cristiana Didilescu  5 , Carolina Constantin  6   7 , Monica Neagu  6   7   8
Affiliations
Review

Capsaicin: Effects on the Pathogenesis of Hepatocellular Carcinoma

Cristian Scheau et al. Molecules. .

Abstract

Hepatocellular carcinoma (HCC) is one of the most frequent cancers, and to date, there have been very few drugs available that can improve survival, the most well-known being sorafenib. The pathogenesis of HCC is complex, involving multiple processes including abnormal cell and tissue regeneration, angiogenesis, genomic instability, cellular proliferation, and signaling pathway alterations. Capsaicin is a substance that holds increasingly high interest and is studied as a therapeutic option in a wide array of diseases. Several studies have investigated capsaicin roles in various stages of HCC oncogenesis. This paper aims to thoroughly detail the available information on the individual effects of capsaicin on the cellular mechanisms and pathways involved in HCC development, as well as investigate their possible cooperation and interferences. The synergistic antitumor effects of capsaicin and sorafenib are also addressed.

Keywords: apoptosis; autophagy; capsaicin; hepatocellular carcinoma; oxidative stress; pathogenesis; regeneration; signaling pathways; tumorigenesis.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
The chemical structure of capsaicin.
Figure 2
Figure 2
The chemical structure of Sorafenib.
Figure 3
Figure 3
Synthetic depiction of the involvement of capsaicin in the mechanisms of hepatocellular carcinoma (HCC) cells’ apoptosis. Major pathways include endoplasmic reticulum (ER) stress, with subsequent activation of B-cell lymphoma 2 (Bcl-2) proteins through c-Jun N-terminal kinase (JNK) pathway, as well as mitochondrial reactive oxygen species (ROS) formation due to calcium inflow, which determines ceramide accumulation. Also, apoptosis is achieved by the inhibition of tumor-associated NOX (tNOX) and promoting the signal transducer and activator of transcription 3 (STAT3) expression, as well as mitochondrial caspase-3 release. Increased Bcl-2 levels will decrease cytochrome c (cc) concentrations, preventing apoptosis.
Figure 4
Figure 4
Synthetic depiction of the involvement of capsaicin in the mechanisms of HCC cells’ autophagy. Major pathways include endoplasmic reticulum (ER) stress, with subsequent activation of B-cell lymphoma 2 (Bcl-2) proteins through c-Jun N-terminal kinase (JNK) pathway, as well as the modulation of epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway. Also, autophagy may be achieved through autophagosome stimulation through the lipid modified form of microtubule-associated proteins 1A/1B light chain 3B (LC3-II) stimulation and promoting peroxisome proliferator-activated receptor gamma (PPAR-δ) and GANT61 expression. Mitochondrial reactive oxygen species (ROS) formation due to calcium inflow will induce an increase of p53, which subsequently will target the Bcl-2/Beclin 1 pathway, leading to autophagy. The accumulation of p62 may also lead to autophagy.
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