Metformin and 4SC‐202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma
Abstract Oral squamous cell carcinoma (OSCC) is the most common and aggressive epithelial tumor in the head and neck region with a rising incidence. Despite the advances in basic science and clinical research, the overall survival rate of OSCC remains low. Thus finding novel effective therapeutic agents for OSCC is necessary. In this study, we investigated the effects and mechanisms of combined metformin and 4SC‐202 in OSCC. Our results showed that metformin and 4SC‐202 synergistically suppressed the proliferation and promoted the intrinsic apoptosis of OSCC cells in vitro and in vivo. Importantly, the proteasome inhibitor MG132 impeded the ΔNp63‐decreasing effects after metformin and 4SC‐202 treatment, indicating that metformin and 4SC‐202 could promote the degradation of ΔNp63 protein. Moreover, ubiquitination level of ΔNp63 increased after metformin or/and 4SC‐202 administration. Furthermore, we revealed that ΔNp63 mediated anticancer effects of metformin and 4SC‐202, as overexpression or suppression of ΔNp63 could attenuate or facilitate the apoptosis rate of OSCC under metformin or/and 4SC‐202 treatment. Collectively, metformin and 4SC‐202 synergistically promote intrinsic apoptosis through accelerating ubiquitin‐mediated degradation of ΔNp63 in OSCC, and this co‐treatment can serve as a potential therapeutic scheme for OSCC..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Cancer Medicine - 8(2019), 7, Seite 3479-3490 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yuan He [VerfasserIn] |
|---|
| Links: |
doi.org [kostenfrei] |
|---|
| Themen: |
ΔNp63 |
|---|
| doi: |
10.1002/cam4.2206 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
DOAJ039808696 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ039808696 | ||
| 003 | DE-627 | ||
| 005 | 20230503111155.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230227s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/cam4.2206 |2 doi | |
| 035 | |a (DE-627)DOAJ039808696 | ||
| 035 | |a (DE-599)DOAJd4044efa94e34b3290a4908afc51351a | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a RC254-282 | |
| 100 | 0 | |a Yuan He |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Metformin and 4SC‐202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Oral squamous cell carcinoma (OSCC) is the most common and aggressive epithelial tumor in the head and neck region with a rising incidence. Despite the advances in basic science and clinical research, the overall survival rate of OSCC remains low. Thus finding novel effective therapeutic agents for OSCC is necessary. In this study, we investigated the effects and mechanisms of combined metformin and 4SC‐202 in OSCC. Our results showed that metformin and 4SC‐202 synergistically suppressed the proliferation and promoted the intrinsic apoptosis of OSCC cells in vitro and in vivo. Importantly, the proteasome inhibitor MG132 impeded the ΔNp63‐decreasing effects after metformin and 4SC‐202 treatment, indicating that metformin and 4SC‐202 could promote the degradation of ΔNp63 protein. Moreover, ubiquitination level of ΔNp63 increased after metformin or/and 4SC‐202 administration. Furthermore, we revealed that ΔNp63 mediated anticancer effects of metformin and 4SC‐202, as overexpression or suppression of ΔNp63 could attenuate or facilitate the apoptosis rate of OSCC under metformin or/and 4SC‐202 treatment. Collectively, metformin and 4SC‐202 synergistically promote intrinsic apoptosis through accelerating ubiquitin‐mediated degradation of ΔNp63 in OSCC, and this co‐treatment can serve as a potential therapeutic scheme for OSCC. | ||
| 650 | 4 | |a 4SC‐202 | |
| 650 | 4 | |a apoptosis | |
| 650 | 4 | |a metformin | |
| 650 | 4 | |a oral squamous cell carcinoma | |
| 650 | 4 | |a ΔNp63 | |
| 653 | 0 | |a Neoplasms. Tumors. Oncology. Including cancer and carcinogens | |
| 700 | 0 | |a Shanshan Tai |e verfasserin |4 aut | |
| 700 | 0 | |a Miao Deng |e verfasserin |4 aut | |
| 700 | 0 | |a Zhaona Fan |e verfasserin |4 aut | |
| 700 | 0 | |a Fan Ping |e verfasserin |4 aut | |
| 700 | 0 | |a Lihong He |e verfasserin |4 aut | |
| 700 | 0 | |a Chi Zhang |e verfasserin |4 aut | |
| 700 | 0 | |a Yulei Huang |e verfasserin |4 aut | |
| 700 | 0 | |a Bin Cheng |e verfasserin |4 aut | |
| 700 | 0 | |a Juan Xia |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Cancer Medicine |d Wiley, 2012 |g 8(2019), 7, Seite 3479-3490 |w (DE-627)DOAJ00006047X |x 20457634 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:2019 |g number:7 |g pages:3479-3490 |
| 856 | 4 | 0 | |u https://doi.org/10.1002/cam4.2206 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/d4044efa94e34b3290a4908afc51351a |z kostenfrei |
| 856 | 4 | 0 | |u https://doi.org/10.1002/cam4.2206 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/2045-7634 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 2019 |e 7 |h 3479-3490 | ||