Prevention of carcinogen-induced oral cancers by polymeric black tea polyphenols via modulation of EGFR-Akt-mTOR pathway.

Autor: Nimbalkar VK; Mahimkar Lab, Cancer Research Institute (CRI), Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai, 410 210, India.; Homi Bhabha National Institute, Training school complex, Anushakti Nagar, Mumbai, 400085, India., Gangar J; Mahimkar Lab, Cancer Research Institute (CRI), Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai, 410 210, India., Shai S; Mahimkar Lab, Cancer Research Institute (CRI), Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai, 410 210, India., Rane P; Homi Bhabha National Institute, Training school complex, Anushakti Nagar, Mumbai, 400085, India.; Clinical Research Secretariat, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India., Mohanta SK; Homi Bhabha National Institute, Training school complex, Anushakti Nagar, Mumbai, 400085, India.; Clinical Research Secretariat, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India., Kannan S; Homi Bhabha National Institute, Training school complex, Anushakti Nagar, Mumbai, 400085, India.; Clinical Research Secretariat, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India., Ingle A; Homi Bhabha National Institute, Training school complex, Anushakti Nagar, Mumbai, 400085, India.; Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai, India., Mittal N; Homi Bhabha National Institute, Training school complex, Anushakti Nagar, Mumbai, 400085, India.; Department of Pathology, Tata Memorial Hospital, Tata Memorial Centre (TMC), Parel, Mumbai, India., Rane S; Homi Bhabha National Institute, Training school complex, Anushakti Nagar, Mumbai, 400085, India.; Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai, India., Mahimkar MB; Mahimkar Lab, Cancer Research Institute (CRI), Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai, 410 210, India. mmahimkar@actrec.gov.in.; Homi Bhabha National Institute, Training school complex, Anushakti Nagar, Mumbai, 400085, India. mmahimkar@actrec.gov.in.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Aug 25; Vol. 12 (1), pp. 14516. Date of Electronic Publication: 2022 Aug 25.
DOI: 10.1038/s41598-022-18680-0
Abstrakt: The overexpression of Epidermal Growth Factor Receptor (EGFR) and dysregulation of its downstream effector pathways are important molecular hallmarks of oral cancers. Present study investigates the chemopreventive potential of polymeric black tea polyphenols (PBPs)/thearubigins (TRs) in the hamster model of oral carcinogenesis as well as determine the effect of PBPs on EGFR and the molecular players in the EGFR pathway. In dose-dependent manner, pre and concurrent treatment with PBPs (1.5%, 5%, 10%) decreased the number and volume of macroscopic tumors as well as the number and area of microscopic lesions. Interestingly, at 10% dose of PBPs, no macroscopic or microscopic tumors were observed. We observed PBPs mediated dose-dependent decrease in oxidative DNA damage (8OHdG); inflammation (COX-2); proliferation (PCNA, Cyclin D1); expression of EGFR, and its downstream signaling kinases (pAkt, Akt, and mTOR); hypoxia (HIF1α) and angiogenesis (VEGF). There was also a PBPs mediated dose-dependent increase in apoptosis (Bax). Thus, our data clearly indicate that the observed chemopreventive potential of PBPs was due to modulation in the EGFR pathway associated with cell proliferation, hypoxia, and angiogenesis. Taken together, our results demonstrate preclinical chemopreventive efficacy of PBPs and give an insight into its mechanistic role in the chemoprevention of experimental oral cancer.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje