The in Vitro and in Vivo Depigmentation Activity of Coenzyme Q, a Major Quinone Derivative from Antrodia Camphorata, Through Autophagy Induction in Human Melanocytes and Keratinocytes

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2024 Feb 26

PMID 38408981

Authors

You-Cheng Hseu

Jou-Tsen Yeh

Chithravel Vadivalagan

Siang-Jyun Chen

Yugandhar Vudhya Gowrisankar

Sudhir Pandey

Yuan-Tai Hsu

Hung-Rong Yen

Hui-Chi Huang

Jhih-Hsuan Hseu

Hsin-Ling Yang

Affiliations

Soon will be listed here.

Abstract

Background: Coenzyme Q (CoQ), a novel quinone derivative of Antrodia camphorata, has been utilized as a therapeutic agent (including antioxidant, anti-inflammatory, antiangiogenic, antiatherosclerotic, and anticancer agents); however, its depigmenting efficiency has yet to be studied.

Methods: We resolved the depigmenting efficiency of CoQ through autophagy induction in melanoma (B16F10) and melanin-feeding keratinocyte (HaCaT) cells and in vivo Zebrafish model. Then, MPLC/HPLC analysis, MTT assay, Western blotting, immunofluorescence staining, LC3 transfection, melanin formation, GFP-LC3 puncta, AVO formation, tyrosinase activity, and TEM were used.

Results: CoQ-induced autophagy in B16F10 cells was shown by enhanced LC3-II accumulation, ATG7 expression, autophagosome GFP-LC3 puncta, and AVOs formation, and ATG4B downregulation, and Beclin-1/Bcl-2 dysregulation. In α-MSH-stimulated B16F10 cells, CoQ induced antimelanogenesis by suppressing CREB-MITF pathway, tyrosinase expression/activity, and melanin formation via autophagy. TEM data disclosed that CoQ increased melanosome-engulfing autophagosomes and autolysosomes in α-MSH-stimulated B16F10 cells. CoQ-inhibited melanogenesis in α-MSH-stimulated B16F10 cells was reversed by pretreatment with the autophagy inhibitor 3-MA or silencing of LC3. Additionally, CoQ-induced autophagy in HaCaT cells was revealed by enhanced LC3-II accumulation, autophagosome GFP-LC3 puncta and AVO formation, ATG4B downregulation, ATG5/ATG7 expression, and Beclin-1/Bcl-2 dysregulation. In melanin-feeding HaCaT cells, CoQ induced melanin degradation by suppressing melanosome gp100 and melanin formation via autophagy. TEM confirmed that CoQ increased melanosome-engulfing autophagosomes and autolysosomes in melanin-feeding HaCaT cells. Treatment with 3-MA reversed CoQ-mediated melanin degradation in melanin-feeding HaCaT cells. In vivo study showed that CoQ suppressed endogenous body pigmentation by antimelanogenesis and melanin degradation through autophagy induction in a zebrafish model.

Conclusions: Our results showed that CoQ exerted antimelanogenesis and melanin degradation by inducing autophagy. CoQ could be used in skin-whitening formulations as a topical cosmetic application.

References

Geethangili M, Tzeng Y . Review of Pharmacological Effects of Antrodia camphorata and Its Bioactive Compounds. Evid Based Complement Alternat Med. 2009; 2011:212641. PMC: 3095428. DOI: 10.1093/ecam/nep108. View

Zhang C, Gruber F, Ni C, Mildner M, Koenig U, Karner S . Suppression of autophagy dysregulates the antioxidant response and causes premature senescence of melanocytes. J Invest Dermatol. 2014; 135(5):1348-1357. DOI: 10.1038/jid.2014.439. View

Hseu Y, Ho Y, Mathew D, Yen H, Chen X, Yang H . The in vitro and in vivo depigmenting activity of Coenzyme Q10 through the down-regulation of α-MSH signaling pathways and induction of Nrf2/ARE-mediated antioxidant genes in UVA-irradiated skin keratinocytes. Biochem Pharmacol. 2019; 164:299-310. DOI: 10.1016/j.bcp.2019.04.015. View

Mizushima N, Komatsu M . Autophagy: renovation of cells and tissues. Cell. 2011; 147(4):728-41. DOI: 10.1016/j.cell.2011.10.026. View

Yang H, Thiyagarajan V, Shen P, Mathew D, Lin K, Liao J . Anti-EMT properties of CoQ0 attributed to PI3K/AKT/NFKB/MMP-9 signaling pathway through ROS-mediated apoptosis. J Exp Clin Cancer Res. 2019; 38(1):186. PMC: 6505074. DOI: 10.1186/s13046-019-1196-x. View

Yang H, Hseu Y, Chen J, Yech Y, Lu F, Wang H . Antrodia camphorata in submerged culture protects low density lipoproteins against oxidative modification. Am J Chin Med. 2006; 34(2):217-31. DOI: 10.1142/S0192415X06003783. View

Xiong J . Atg7 in development and disease: panacea or Pandora's Box?. Protein Cell. 2015; 6(10):722-34. PMC: 4598325. DOI: 10.1007/s13238-015-0195-8. View

Cawley N, Li Z, Loh Y . 60 YEARS OF POMC: Biosynthesis, trafficking, and secretion of pro-opiomelanocortin-derived peptides. J Mol Endocrinol. 2016; 56(4):T77-97. PMC: 4899099. DOI: 10.1530/JME-15-0323. View

Siridechakorn I, Pimpa J, Choodej S, Ngamrojanavanich N, Pudhom K . Synergistic impact of arbutin and kaempferol-7-O-α-L-rhamnopyranoside from Nephelium lappaceum L. on whitening efficacy and stability of cosmetic formulations. Sci Rep. 2023; 13(1):22004. PMC: 10716148. DOI: 10.1038/s41598-023-49351-3. View

10.

Lee K, Kim M, Lee S, Kim K . The Function of Autophagy as a Regulator of Melanin Homeostasis. Cells. 2022; 11(13). PMC: 9265842. DOI: 10.3390/cells11132085. View

11.

Perdomo J, Quintana C, Gonzalez I, Hernandez I, Rubio S, Loro J . Melatonin Induces Melanogenesis in Human SK-MEL-1 Melanoma Cells Involving Glycogen Synthase Kinase-3 and Reactive Oxygen Species. Int J Mol Sci. 2020; 21(14). PMC: 7404125. DOI: 10.3390/ijms21144970. View

12.

Funderburk S, Wang Q, Yue Z . The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond. Trends Cell Biol. 2010; 20(6):355-62. PMC: 3781210. DOI: 10.1016/j.tcb.2010.03.002. View

13.

Abdel-Malek Z, Scott M, Suzuki I, Tada A, Im S, Lamoreux L . The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation. Pigment Cell Res. 2000; 13 Suppl 8:156-62. DOI: 10.1034/j.1600-0749.13.s8.28.x. View

14.

Nordin F, Aziz A, Zakaria Z, Wan Mohamed Radzi C . A systematic review on the skin whitening products and their ingredients for safety, health risk, and the halal status. J Cosmet Dermatol. 2020; 20(4):1050-1060. DOI: 10.1111/jocd.13691. View

15.

Hseu Y, Chao Y, Lin K, Way T, Lin H, Thiyagarajan V . Antrodia camphorata inhibits metastasis and epithelial-to-mesenchymal transition via the modulation of claudin-1 and Wnt/β-catenin signaling pathways in human colon cancer cells. J Ethnopharmacol. 2017; 208:72-83. DOI: 10.1016/j.jep.2017.07.001. View

16.

Swope V, Abdel-Malek Z . MC1R: Front and Center in the Bright Side of Dark Eumelanin and DNA Repair. Int J Mol Sci. 2018; 19(9). PMC: 6163888. DOI: 10.3390/ijms19092667. View

17.

Zolghadri S, Bahrami A, Khan M, Munoz-Munoz J, Garcia-Molina F, Garcia-Canovas F . A comprehensive review on tyrosinase inhibitors. J Enzyme Inhib Med Chem. 2019; 34(1):279-309. PMC: 6327992. DOI: 10.1080/14756366.2018.1545767. View

18.

Yang Z, Wilkie-Grantham R, Yanagi T, Shu C, Matsuzawa S, Reed J . ATG4B (Autophagin-1) phosphorylation modulates autophagy. J Biol Chem. 2015; 290(44):26549-61. PMC: 4646313. DOI: 10.1074/jbc.M115.658088. View

19.

Hseu Y, Chen X, Gowrisankar Y, Yen H, Chuang J, Yang H . The Skin-Whitening Effects of Ectoine via the Suppression of α-MSH-Stimulated Melanogenesis and the Activation of Antioxidant Nrf2 Pathways in UVA-Irradiated Keratinocytes. Antioxidants (Basel). 2020; 9(1). PMC: 7022695. DOI: 10.3390/antiox9010063. View

20.

Otomo C, Metlagel Z, Takaesu G, Otomo T . Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. Nat Struct Mol Biol. 2012; 20(1):59-66. PMC: 3540207. DOI: 10.1038/nsmb.2431. View