Background/Aim: Pyruvate kinase M2 (PKM2) is an enzyme that is predominantly overexpressed in various types of cancer. The role of PKM2 in liver fluke-associated cholangiocarcinoma (CCA) remains unclear. This study aimed to investigate the antitumor activity of shikonin, a PKM2 inhibitor, in CCA cells. Materials and Methods: Immunohistochemistry and immunoblotting were used to determine PKM2 expression in CCA tissues and cells. Antiproliferative effects of shikonin were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony-formation and trypan blue exclusion assays. The antimetastatic activity of shikonin was determined using the Boyden chamber assay. Mechanisms by which shikonin inhibited CCA progression were determined. Results: PKM2 was overexpressed in CCA compared to normal bile duct epithelial cells. Shikonin significantly inhibited growth, and migration of CCA cells while inducing their death. A mechanistic study revealed that antitumor effects of shikonin in CCA cells depended on increased production of reactive oxygen species. Conclusion: Shikonin may be a novel therapeutic agent for patients with CCA. Cholangiocarcinoma (CCA) is an aggressive malignancy which originates from bile duct epithelia. The highest incidence and mortality rate of CCA was found in Southeast Asian countries, especially in northeastern Thailand (1). Recent epidemiological studies indicated that the incidence of CCA is different according to geographical risk factors and genetic backgrounds. Thamavit et al. showed that the infection with liver fluke, namely Opisthorchis viverrini (OV), is strongly associated with CCA development in Thailand, an area in which OV is endemic (2). Most patients with CCA present with an advanced stage of the disease, leading to a late diagnosis, poor prognosis and a short survival (3). Although surgical resection has remained a good choice for CCA therapy, only a very small number of cases can be operated on and this results in a high recurrence. At present, few neoadjuvant or adjuvant treatments for CCA are available as treatment options for patients with unresectable CCA or for after surgery. Chemoresistance and tumor relapse are still high in patients with CCA (4). Therefore, a new effective therapeutic agent for CCA is needed. Metabolic reprogramming, first described by Hanahan and Weinberg, is a cancer hallmark (5). Most cancer cells prefer to use aerobic glycolysis than mitochondrial metabolism; this is known as the Warburg effect. Up-regulation of glycolytic enzymes have been reported in several cancer types including CCA, suggesting that these enzymes are potential targets for diagnosis and therapy of cancer (6). Pyruvate kinase M2 (PKM2), a key enzyme in the glycolytic pathway, is an isomeric form of pyruvate kinase, occurring in four isoforms: R, L, M1, and M2. PKM2 exhibits two major states, one is a highly active state in the tetrameric form and the other is the less active state in the dimeric form (7). Dimeric PKM2 facilitates the production of glycolytic int...

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Skin hyperpigmentation is an aesthetic problem that leads to psychosocial issues. Thus, skin whitening agents from agro- and poultry-industrial co-products are considered high economic value ingredients of interest for sustainable application. Therefore, this study aimed to determine the cosmeceutical potential of anserine/carnosine-rich chicken extract (ACCE) from the Thai native chicken Pradu Hang Dam Mor Kor 55 (PD) meat. The chemical composition was identified and quantified using the HPLC-UV method. Then, the antioxidation potential of the extract was compared to that of L-anserine and L-carnosine, using 1,1-diphenyl-2-picrylhydrazyl assay and shikonin-induced production of reactive oxygen species in CCD-986Sk cell models, and the anti-melanogenesis effect in the MNT-1 melanoma cell line model was investigated. Furthermore, related mechanisms were identified using colorimetric tyrosinase assay and the Western blot technique. The ACCE was composed of L-anserine and L-carnosine as two major constituents. In a dose-dependent manner, ACCE, L-anserine, and L-carnosine manifested significant antioxidation potential and significant reduction of melanin production. Activation of the extracellular signal-regulated kinase (ERK) signaling pathway and inhibition of tyrosinase activity of ACCE were demonstrated as the mechanisms of the anti-melanogenesis effect. In conclusion, ACCE has been revealed as a potential cosmeceutical agent due to its antioxidation and anti-melanogenic activity in association with L-anserine and L-carnosine composition and biomolecular regulating ability. Therefore, further studies and development should be considered to support the utilization of anserine/carnosine-rich chicken extract in the cosmetic industry for economic value creation and sustainability.