Topical GZ21T Inhibits the Growth of Actinic Keratoses in a UVB-Induced Model of Skin Carcinogenesis
Actinic keratoses (AKs) are premalignant intraepidermal neoplasms that occur as a result of cumulative sun damage. AKs commonly relapse, and up to 16% undergo malignant transformation into cutaneous squamous cell carcinoma. There is a need for novel therapies that reduce the quantity and surface are...
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| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Book |
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Elsevier,
2023-07-01T00:00:00Z.
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| 001 | doaj_d8bb68c735b44d65b789dbe48f8f897b | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Zachary A. Bordeaux |e author |
| 700 | 1 | 0 | |a Justin Choi |e author |
| 700 | 1 | 0 | |a Gabriella Braun |e author |
| 700 | 1 | 0 | |a Cole Davis |e author |
| 700 | 1 | 0 | |a Melika Marani |e author |
| 700 | 1 | 0 | |a Kevin Lee |e author |
| 700 | 1 | 0 | |a Christeen Samuel |e author |
| 700 | 1 | 0 | |a Jackson Adams |e author |
| 700 | 1 | 0 | |a Reed Windom |e author |
| 700 | 1 | 0 | |a Anthony Pollizzi |e author |
| 700 | 1 | 0 | |a Anusha Kambala |e author |
| 700 | 1 | 0 | |a Hannah Cornman |e author |
| 700 | 1 | 0 | |a Sriya V. Reddy |e author |
| 700 | 1 | 0 | |a Weiying Lu |e author |
| 700 | 1 | 0 | |a Olusola O. Oladipo |e author |
| 700 | 1 | 0 | |a Martin P. Alphonse |e author |
| 700 | 1 | 0 | |a Cameron E. West |e author |
| 700 | 1 | 0 | |a Shawn G. Kwatra |e author |
| 700 | 1 | 0 | |a Madan M. Kwatra |e author |
| 245 | 0 | 0 | |a Topical GZ21T Inhibits the Growth of Actinic Keratoses in a UVB-Induced Model of Skin Carcinogenesis |
| 260 | |b Elsevier, |c 2023-07-01T00:00:00Z. | ||
| 500 | |a 2667-0267 | ||
| 500 | |a 10.1016/j.xjidi.2023.100206 | ||
| 520 | |a Actinic keratoses (AKs) are premalignant intraepidermal neoplasms that occur as a result of cumulative sun damage. AKs commonly relapse, and up to 16% undergo malignant transformation into cutaneous squamous cell carcinoma. There is a need for novel therapies that reduce the quantity and surface area of AKs as well as prevent malignant transformation to cutaneous squamous cell carcinomas. We recently showed that GZ17-6.02, an anticancer agent composed of curcumin, haramine, and isovanillin, inhibited the growth of H297.T cells. This study evaluated the efficacy of a topical formulation of GZ17-6.02, known as GZ21T, in a murine model of AK generated by exposing SKH1 mice to UVR. Treatment of mice with topical GZ21T inhibited the growth of AKs by decreasing both lesion count (P = 0.012) and surface area occupied by tumor (P = 0.002). GZ21T also suppressed the progression of AKs to cutaneous squamous cell carcinoma by decreasing the count (P = 0.047) and surface area (P = 0.049) of lesions more likely to represent cutaneous squamous cell carcinoma. RNA sequencing and proteomic analyses revealed that GZ21T suppressed several pathways, including MAPK (P = 0.025), phosphoinositide 3-kinase-protein kinase B (P = 0.04), HIF-1α (P = 0.016), Wnt (P = 0.025), insulin (P = 0.018), and ERBB (P = 0.016) signaling. GZ21T also upregulated the autophagy-promoting protein AMPK while suppressing proteins such as PD-L1, glutaminase, pAkt1 S473, and eEF2K. | ||
| 546 | |a EN | ||
| 690 | |a Dermatology | ||
| 690 | |a RL1-803 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n JID Innovations, Vol 3, Iss 4, Pp 100206- (2023) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S2667026723000292 | |
| 787 | 0 | |n https://doaj.org/toc/2667-0267 | |
| 856 | 4 | 1 | |u https://doaj.org/article/d8bb68c735b44d65b789dbe48f8f897b |z Connect to this object online. |