Thymol inhibits oral squamous cell carcinoma growth via mitochondria‐mediated apoptosis

Chapa, Jorge J. De La; Singha, Prajjal K.; Lee, Debbie R.; Gonzales, Cara B.

doi:10.1111/jop.12735

Cited by 55 publications

(44 citation statements)

References 26 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thymol is a transient receptor potential ankyrin subtype 1 (TRPA1) channel, agonist found in thyme (Thymus vulgaris) and oregano (Origanum vulgare). In oral squamous cell carcinoma Cal27-and HeLa-derived mouse xenografts, intratumor injection of thymol (4.3 mmol/L) reduced the tumor volume with decreasing cell proliferation and inducing apoptosis as observed by Ki-67 staining and TUNEL assays, respectively (De La Chapa et al, 2018). The in vitro molecular mechanism studies showed that thymol induced depolarization of mitochondrial membrane potential to induce apoptosis (De La Chapa et al, 2018).…”

Section: Phytochemicals In Pre-clinical Trialsmentioning

confidence: 99%

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

et al. 2020

View full text Add to dashboard Cite

Cancer is a severe health problem that continues to be a leading cause of death worldwide. Increasing knowledge of the molecular mechanisms underlying cancer progression has led to the development of a vast number of anticancer drugs. However, the use of chemically synthesized drugs has not significantly improved the overall survival rate over the past few decades. As a result, new strategies and novel chemoprevention agents are needed to complement current cancer therapies to improve efficiency. Naturally occurring compounds from plants known as phytochemicals, serve as vital resources for novel drugs and are also sources for cancer therapy. Some typical examples include taxol analogs, vinca alkaloids such as vincristine, vinblastine, and podophyllotoxin analogs. These phytochemicals often act via regulating molecular pathways which are implicated in growth and progression of cancer. The specific mechanisms include increasing antioxidant status, carcinogen inactivation, inhibiting proliferation, induction of cell cycle arrest and apoptosis; and regulation of the immune system. The primary objective of this review is to describe what we know to date of the active compounds in the natural products, along with their pharmacologic action and molecular or specific targets. Recent trends and gaps in phytochemical based anticancer drug discovery are also explored. The authors wish to expand the phytochemical research area not only for their scientific soundness but also for their potential druggability. Hence, the emphasis is given to information about anticancer phytochemicals which are evaluated at preclinical and clinical level.

show abstract

Section: Phytochemicals In Pre-clinical Trialsmentioning

confidence: 99%

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

et al. 2020

View full text Add to dashboard Cite

show abstract

“…JC‐1 assays were performed as previously described . Cells were treated for 2 hours with analogs or vehicle control (n = 3 per group) at the indicated concentrations and stained with 1 μmol/L JC‐1 dye (Thermo Fisher Scientific, Waltham, MA, USA) for 15 minutes at 37°C.…”

Section: Methodsmentioning

confidence: 99%

The novel capsazepine analog, CIDD‐99, significantly inhibits oral squamous cell carcinoma in vivo through a TRPV1‐independent induction of ER stress, mitochondrial dysfunction, and apoptosis

Chapa

Singha

Self

et al. 2019

J Oral Pathology Medicine

Self Cite

View full text Add to dashboard Cite

Background Oral squamous cell carcinoma (OSCC) is a deadly disease with a mere 40% five‐year survival rate for patients with advanced disease. Previously, we discovered that capsazepine (CPZ), a transient receptor potential channel, Vanilloid subtype 1 (TRPV1) antagonist, has significant anti‐tumor effects against OSCC via a unique mechanism‐of‐action that is independent of TRPV1. Thus, we developed novel CPZ analogs with more potent anti‐proliferative effects (CIDD‐24, CIDD‐99, and CIDD‐111). Methods Using OSCC xenograft models, we determined the efficacy of these analogs in vivo. TRPV1 interactions were evaluated using calcium imaging and a rat model of orofacial pain. Anti‐cancer mechanism(s)‐of‐action were assessed by cell cycle analysis and mitochondrial depolarization assays. Results CIDD‐99 was the most potent analog demonstrating significant anti‐tumor effects in vivo (P < 0.001). CIDD‐24 was equipotent to the parent compound CPZ, but less potent than CIDD‐99. CIDD‐111 was the least efficacious analog. Calcium imaging studies confirmed that CIDD‐99 neither activates nor inhibits TRPV1 confirming that TRPV1 activity is not involved in its anti‐cancer effects. All analogs induced an S‐phase block, dose‐dependent mitochondrial depolarization, and apoptosis. Histological analyses revealed increased apoptosis and reduced cell proliferation in tumors treated with these analogs. Importantly, CIDD‐99 had the most dramatic anti‐tumor effects with 85% of tumors resolving leaving only minute traces of viable tissue. Additionally, CIDD‐99 was non‐noxious and demonstrated no observable adverse reactions Conclusion This study describes a novel, highly efficacious, CPZ analog, CIDD‐99, with dramatic anti‐tumor effects against OSCC that may be efficacious as a lone therapy or in combination with standard therapies.

show abstract

“…Most of the Inula metabolites tested were sesquiterpenolides. On the other hand, thymol and thymol derivatives as well as extracts and essential oils containing these compounds [61][62][63][64] are known to be cytotoxic. These results suggest that the H extract induced a significant activation of a p21-dependent, p53-independent pathway in OCI-AML3 cells and that compound 2 was responsible of this activity and the associated cell cycle arrest.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Bioassay-Guided Isolation of Antiproliferative Compounds from Limbarda crithmoides (L.) Dumort

et al. 2020

View full text Add to dashboard Cite

Limbarda crithmoides (L.) Dumort (Asteraceae) n-hexane extract displayed high cell proliferation inhibitory activity against acute myeloid leukaemia cells (OCI-AML3) and was therefore subjected to a bioassay-guided multistep separation procedure. Two thymol derivatives, namely 10-acetoxy-8,9-epoxythymol tiglate (1) and 10-acetoxy-9-chloro-8,9-dehydrothymol (2), were isolated and identified by means of NMR spectroscopy. Both of them exhibited a significant dose-dependent inhibition of cell proliferation.

show abstract

Thymol inhibits oral squamous cell carcinoma growth via mitochondria‐mediated apoptosis

Abstract: Our findings provide the first evidence of thymol's novel antitumor effects against OSCC in vivo, which do not rely on TRPA1 activity. Instead, we show that thymol induces mitochondrial dysfunction and apoptosis and may be efficacious against multiple cancers.

Cited by 55 publications

References 26 publications

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

The novel capsazepine analog, CIDD‐99, significantly inhibits oral squamous cell carcinoma in vivo through a TRPV1‐independent induction of ER stress, mitochondrial dysfunction, and apoptosis

Bioassay-Guided Isolation of Antiproliferative Compounds from Limbarda crithmoides (L.) Dumort

Contact Info

Product

Resources

About