المؤلفون: Beesetti, Swarnalatha, Surabhi, Rohan P., Rayala, Suresh K., Venkatraman, Ganesh

المصدر: Journal of Cellular Physiology; Jan2019, Vol. 234 Issue 1, p969-975, 7p

مصطلحات موضوعية: SKIN cancer, ULTRAVIOLET radiation, EPIDERMAL growth factor receptors, KERATINOCYTES, DNA damage

مستخلص: Despite regular exposure of skin to solar UV‐B irradiation, most individuals enjoy cancer‐free existence, which is a testimony of the inherent capacity of human keratinocytes to either repair or restore cells damged by UV exposure. In this manuscript, we focus on delineating the mechanistic role of p21 activated kinase (Pak1) in UV‐B provoked skin lesions. Molecular mechanistic studies revealed that Pak1 is triggered as a consequence to UV‐B exposure via epidermal growth factor receptor (EGFR) and cyclobutane pyrimidine dimers (CPD) pathways, and both these membranous (EGFR) and nuclear (CPDs) events converge at Pak1 activation and contribute in a coordinated manner for yielding a complete response to UV‐B via upregulating Ataxia–Telangiectasia and Rad3 related (ATR). This is the first study that evaluates the mechanistic role of a signaling molecule, Pak1, in premalignant skin lesions caused by sun exposure and designate that expression and instigation of Pak1 could operate as an alarming indicator of succession towards aggressive form of skin cancer, if neglected. The current study evaluates the mechanistic role of a signaling molecule, P21 activated kinase‐1 in premalignant skin lesions caused by sun exposure. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Cellular Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Tentu, Shilpa, Nandarapu, Kumarswamyreddy, Muthuraj, Prakash, Venkitasamy, Kesavan, Venkatraman, Ganesh, Rayala, Suresh K.

المصدر: Journal of Cellular Physiology; Mar2018, Vol. 233 Issue 3, p2613-2628, 16p

مصطلحات موضوعية: TRANSCRIPTION factors, ANTINEOPLASTIC agents, HEAD & neck cancer, CHEMICAL derivatives, POLYMERASE chain reaction, SQUAMOUS cell carcinoma

مستخلص: A series of 2, 3-dihydroquinazolinone derivatives were synthesized, characterized and their anticancer activity was determined. Among the compounds synthesized and screened, one compound ( 17) showed potent anticancer activity against human head and neck squamous cell carcinoma cell line, SCC131 and was non-toxic to normal cells. The compound inhibited the growth of SCC131 cells, with an IC50 of 1.75 μM, triggered apoptotic mode of cell death and caused tumor regression of SCC131 tumor xenografts in athymic mice. To decipher the target for the lead compound, a high throughput qPCR array was performed. Results showed that the compound 17, inhibited the expression of a vital transcription factor HNF4A, involved in regulation of metabolic pathways. Thus, the present work has identified a lead compound 17, with potent anticancer activity, minimal normal cell toxicity and a plausible target and hence definitely holds future prospects as an anticancer agent. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Cellular Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)