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Research Paper | Pharmacology Science | India | Volume 11 Issue 11, November 2022
Acetyl-CoA Carboxylase 1 Up-Regulation and Skin Tumor Formation in a Skin Carcinogenesis Mouse Model are Suppressed by Withaferin A.
Sonu Sharma [2] | Shilpa Mamgain | Jyoti Gupta [5]
Abstract: Traditional oriental treatments have employed withaferin A (WA), a natural substance derived from Withania somnifera, to treat neurological diseases. A clinical trial has been started to test WA in treating melanoma in light of recent studies that suggest this molecule may have the capacity to treat cancer. Here, the chemo preventive potential of WA was examined in a mouse model of chemically induced skin carcinogenesis. Pathological analyses showed that WA greatly reduced the development of skin tumours. According to morphological analyses of the skin tissues, WA prevented cell division rather than causing apoptosis during the development of skin cancer. A skin cell transformation model and antibody Micro array analysis both showed that WA prevented acetyl-CoA carboxylase 1 (ACC1) from being up-regulated by carcinogens. Transformable skin cells' anchorage-independent proliferation and oncogene activation were increased by ACC1 overexpression, whereas they were reduced by ACC1 knockdown. Additional research revealed that WA prevented activator protein 1 from becoming activated, which prevented tumour promotor-induced ACC1 gene transcription. WA was similarly effective at reducing ACC1 expression in melanoma cells. The up-regulation of ACC1 in tumours compared to nearby normal tissues was lastly validated by research employing human skin cancer tissues. In conclusion, our findings imply that withaferin A may be useful in chemoprevention and that ACC1 may be an important target of WA. Wiley Periodicals, Inc. 2015
Keywords: withaferin A, skin carcinogenesis, ACC1, cell proliferation, apoptosis
Edition: Volume 11 Issue 11, November 2022,
Pages: 905 - 912