Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy‐lysosome mediated OCT4A degradation

Wu, Liying; Xu, Sheng; Cheng, Xian; Zhang, Li; Wang, Yunping; Wu, Jianli; Bao, Jiandong; Yu, Huixin; Lu, Rongrong

doi:10.1002/ptr.7361

Cited by 9 publications

(4 citation statements)

References 67 publications

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“…Furthermore, capsaicin is involved in the autophagic degradation of OCT4A, a cell stemness regulator. The reduction of stemness can probably ameliorate ATC aggressiveness [ 108 ]. In a word, these agents have great pharmacological and economic benefits, and more translational researches and clinical trials are required in the future.…”

Section: Autophagy Is a Promising Target For Tc Treatmentsmentioning

confidence: 99%

The new insights into autophagy in thyroid cancer progression

2023

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In recent decades, the incidence of thyroid cancer keeps growing at a shocking rate, which has aroused increasing concerns worldwide. Autophagy is a fundamental and ubiquitous biological event conserved in mammals including humans. Basically, autophagy is a catabolic process that cellular components including small molecules and damaged organelles are degraded for recycle to meet the energy needs, especially under the extreme conditions. The dysregulated autophagy has indicated to be involved in thyroid cancer progression. The enhancement of autophagy can lead to autophagic cell death during the degradation while the produced energies can be utilized by the rest of the cancerous tissue, thus this influence could be bidirectional, which plays either a tumor-suppressive or oncogenic role. Accordingly, autophagy can be suppressed by therapeutic agents and is thus regarded as a drug target for thyroid cancer treatments. In the present review, a brief description of autophagy and roles of autophagy in tumor context are given. We have addressed summary of the mechanisms and functions of autophagy in thyroid cancer. Some potential autophagy-targeted treatments are also summarized. The aim of the review is linking autophagy to thyroid cancer, so as to develop novel approaches to better control cancer progression.

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Section: Autophagy Is a Promising Target For Tc Treatmentsmentioning

confidence: 99%

The new insights into autophagy in thyroid cancer progression

2023

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“…In addition, as a natural alkaloid derived from Capsicum spp. [110], Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide, CAP) is a natural alkaloid [110], which inhibits the stemness of mesenchymal TC cells by activating autophagic lysosomal-mediated degradation of OCT4A [111]. The action of CAP on ATC helps us explore new ATC-targeting drugs [108,[112][113][114].…”

Section: The Role Of Inhibitors Substances and Autophagy In Thyroid-r...mentioning

confidence: 99%

Non-Apoptotic Programmed Cell Death in Thyroid Diseases

Qiu

2022

Pharmaceuticals

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Thyroid disorders are among the most common endocrinological conditions. As the prevalence of thyroid diseases increases annually, the exploration of thyroid disease mechanisms and the development of treatments are also gradually improving. With the gradual advancement of therapies, non-apoptotic programmed cell death (NAPCD) has immense potential in inflammatory and neoplastic diseases. Autophagy, pyroptosis, ferroptosis, and immunogenic cell death are all classical NAPCD. In this paper, we have compiled the recent mechanistic investigations of thyroid diseases and established the considerable progress by NAPCD in thyroid diseases. Furthermore, we have elucidated the role of various types of NAPCD in different thyroid disorders. This will help us to better understand the pathophysiology of thyroid-related disorders and identify new targets and mechanisms of drug resistance, which may facilitate the development of novel diagnostic and therapeutic strategies for patients with thyroid diseases. Here, we have reviewed the advances in the role of NAPCD in the occurrence, progression, and prognosis of thyroid diseases, and highlighted future research prospects in this area.

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“…Capsaicin is approved by the FDA for topical use in pain management of arthritis, diabetic neuropathy, and neuralgia and also to treat post-surgical neuropathic pain in cancer patients 32 . Numerous reports have shown that capsaicin induces cell cycle arrest and apoptosis in cancer cell lines 33 and autophagy in anaplastic thyroid carcinoma cells 34 . Interestingly, co-treatment of cancer cells with capsaicin and capsazepine (a TRPV1 antagonist) showed that cells still die by apoptosis 35 , suggesting that cytotoxicity was independent of TRPV1 activation, which was confirmed in an oral cancer model 36 .…”

Section: Introductionmentioning

confidence: 99%

Capsaicin binds the N-terminus of Hsp90, induces lysosomal degradation of Hsp70, and enhances the anti-tumor effects of 17-AAG (Tanespimycin)

Patwardhan,

Kommalapati,

Llbiyi

et al. 2023

Sci Rep

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Heat shock protein 90 (Hsp90) and its co-chaperones promote cancer, and targeting Hsp90 holds promise for cancer treatment. Most of the efforts to harness this potential have focused on targeting the Hsp90 N-terminus ATP binding site. Although newer-generation inhibitors have shown improved efficacy in aggressive cancers, induction of the cellular heat shock response (HSR) by these inhibitors is thought to limit their clinical efficacy. Therefore, Hsp90 inhibitors with novel mechanisms of action and that do not trigger the HSR would be advantageous. Here, we investigated the mechanism by which capsaicin inhibits Hsp90. Through mutagenesis, chemical modifications, and proteomic studies, we show that capsaicin binds to the N-terminus of Hsp90 and inhibits its ATPase activity. Consequently, capsaicin and its analogs inhibit Hsp90 ATPase-dependent progesterone receptor reconstitution in vitro. Capsaicin did not induce the HSR, instead, it promoted the degradation of Hsp70 through the lysosome-autophagy pathway. Remarkably, capsaicin did not induce degradation of the constitutively expressed cognate Hsc70, indicating selectivity for Hsp70. Combined treatments of capsaicin and the Hsp90 inhibitor 17-AAG improved the anti-tumor efficacy of 17-AAG in cell culture and tridimensional tumor spheroid growth assays using breast and prostate cancer models. Consistent with this, in silico docking studies revealed that capsaicin binding to the ATP binding site of Hsp90 was distinct from classical N-terminus Hsp90 inhibitors, indicating a novel mechanism of action. Collectively, these findings support the use of capsaicin as a chemical scaffold to develop novel Hsp90 N-terminus inhibitors as well as its ability to be a potential cancer co-therapeutic.

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Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy‐lysosome mediated OCT4A degradation

Cited by 9 publications

References 67 publications

The new insights into autophagy in thyroid cancer progression

The new insights into autophagy in thyroid cancer progression

Non-Apoptotic Programmed Cell Death in Thyroid Diseases

Capsaicin binds the N-terminus of Hsp90, induces lysosomal degradation of Hsp70, and enhances the anti-tumor effects of 17-AAG (Tanespimycin)

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