Wogonin inhibits the growth of HT144 melanoma via regulating hedgehog signaling-mediated inflammation and glycolysis

Ding

Oxidative Medicine and Cellular Longevity

et al. 2022

Wumei Pill (WMP) is a traditional Chinese herbal formulation and widely used to treat digestive system diseases in clinical. S-Adenosylhomocysteine hydrolase (AHCY) can catalyze the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine in living organisms, and its abnormal expression is linked to the pathogenesis of many diseases including colorectal cancer (CRC). A previous study reported that WMP could prevent CRC in mice; however, the underlying mechanisms especially the roles of AHCY in WMP-induced anti-CRC remain largely unknown. Here, we investigated the regulatory roles and potential mechanisms of AHCY in WMP-induced anti-CRC. WMP notably alleviated the azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colitis-associated colon cancer (CAC) in mice. Besides, WMP inhibited the inflammation and oxidative stress in AOM/DSS-induced CAC mice. AHCY was high expression in clinical samples of colon cancer compared to the adjacent tissues. WMP inhibited the AHCY expression in AOM/DSS-induced CAC mice. An in vitro study found that AHCY overexpression induced cell proliferation, colony formation, invasion, and tumor angiogenesis, whereas its knockdown impaired its oncogenic function. AHCY overexpression enhanced, while its knockdown weakened the inflammation and oxidative stress in colon cancer cells. Interestingly, WMP potently suppressed the hedgehog (Hh) signaling in AOM/DSS-induced CAC mice. A further study showed that AHCY overexpression activated the Hh signaling while AHCY knockdown inactivated the Hh signaling. Moreover, activation of the Hh signaling reversed the effect of AHCY silencing on inflammation and oxidative stress in vitro. In conclusion, WMP alleviated the AOM/DSS-induced CAC through inhibition of inflammation and oxidative stress by regulating AHCY-mediated hedgehog signaling in mice. These findings uncovered a potential molecular mechanism underlying the anti-CAC effect of WMP and suggested WMP as a promising therapeutic candidate for CRC.

Section: Discussionmentioning

confidence: 99%

Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice

Ding

Oxidative Medicine and Cellular Longevity

et al. 2022

“…It is accepted that wogonin has various inhibitory effects in different melanoma cells, including on invasion and migration of B16F10 cells, melanin synthesis in A375 melanoma cells, or the proliferation and tumour growth of HT144 melanoma cells [ 129 , 130 ]. The anti-inflammatory effect of wogonin in HT144 melanoma is supported by the following activities: (i) pro-inflammatory factors decrease, (ii) anti-inflammatory factors increase, and (iii) inflammatory cytokines expression increase [ 131 ]. Additionally, the anti-tumour effects are performed by: (i) glucose consumption decrease; (ii) production of ATP and lactic acid decrease; (iii) kinases’ activities, such as phosphofructokinase (PFK), hexokinase (HK), and pyruvate kinase (PK) inhibition; and (iv) expression of glucose cotransporter-1 (GLUT1), monocarboxylate transporter 1 (MCT-1), and MCT4 inhibition [ 131 ].…”

Section: Inflammatory Microenvironment In Malignant Melanomamentioning

confidence: 99%

The Interplay between Tumour Microenvironment Components in Malignant Melanoma

et al. 2022

Malignant melanoma has shown an increasing incidence during the last two decades, exhibiting a large spectrum of locations and clinicopathological characteristics. Although current histopathological, biochemical, immunohistochemical, and molecular methods provide a deep insight into its biological behaviour and outcome, melanoma is still an unpredictable disease, with poor outcome. This review of the literature is aimed at updating the knowledge regarding melanoma’s clinicopathological and molecular hallmarks, including its heterogeneity and plasticity, involving cancer stem cells population. A special focus is given on the interplay between different cellular components and their secretion products in melanoma, considering its contribution to tumour progression, invasion, metastasis, recurrences, and resistance to classical therapy. Furthermore, the influences of the specific tumour microenvironment or “inflammasome”, its association with adipose tissue products, including the release of “extracellular vesicles”, and distinct microbiota are currently studied, considering their influences on diagnosis and prognosis. An insight into melanoma’s particular features may reveal new molecular pathways which may be exploited in order to develop innovative therapeutic approaches or tailored therapy.

“…The Warburg effect, which is the metabolic shift from energy acquisition primarily through balanced mitochondrial OXPHOS to fast but inefficient aerobic glycolysis, is hypothesized to be an important driver of tumor formation and proliferation (15). HK, PFK and PK, key enzymes in glycolysis, serve important roles in glycolytic metabolism (48,49). Osteosarcoma has a strong glycolytic phenotype and studies have shown that aberrantly expressed molecules, including c-Myc, SLIT2 and ROBO1, in osteosarcoma can inhibit mitochondrial OXPHOS and promote aerobic glycolysis (50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

APOC1 promotes the progression of osteosarcoma by binding to MTCH2

2023

Exp Ther Med