Uterine cervical cancer is a highly prevalent gynecological malignancy that imposes high morbidity and mortality in Sub-Saharan Africa. The extra-skeletal action of the vitamin D family of hormones includes its preventative and therapeutic roles in various cancers—with some promising results in preclinical studies. Vitamin D hormones investigated in cancer research include early precursors (cholecalciferol and 25-hydroxycholecalciferol) and the fully activated 1.25 dihydroxycholecalciferol. The early precursors are activated systemically by the cytochrome P450 (CYP450) family of enzymes in sequential hydroxylation steps in the liver and kidney. Notably, healthy and cancerous uterine cervical tissues express gene and protein levels of vitamin D receptor (VDR) and activating and catabolising vitamin D CYP450 enzymes, collectively comprising the autocrine vitamin D metabolism system (VDMS). Thus, in the uterine cervix, systemic vitamin D metabolism is complemented by the additive autocrine VDMS. The autocrine VDMS axis, therefore, may confer potential anticancer benefits by fine-tuning intracellular vitamin D metabolism involved in the downstream regulation of cell health genes. This chapter includes an overview of uterine cervical cancer and vitamin D metabolism, a brief description of the molecular mechanisms of vitamin D’s anticancer actions and an exploration of preclinical studies which have investigated the role of autocrine VDMS-mediated anti-tumorigenesis in uterine cervical cancer. Additionally, the potential chemotherapeutic implications of autocrine vitamin D metabolism in uterine cervical cancer are considered.

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Autocrine Vitamin D Metabolism Mediates Anticancer Actions in Uterine Cervical Cancer

  • Rivak Punchoo,
  • Sachin Bhoora

摘要

Uterine cervical cancer is a highly prevalent gynecological malignancy that imposes high morbidity and mortality in Sub-Saharan Africa. The extra-skeletal action of the vitamin D family of hormones includes its preventative and therapeutic roles in various cancers—with some promising results in preclinical studies. Vitamin D hormones investigated in cancer research include early precursors (cholecalciferol and 25-hydroxycholecalciferol) and the fully activated 1.25 dihydroxycholecalciferol. The early precursors are activated systemically by the cytochrome P450 (CYP450) family of enzymes in sequential hydroxylation steps in the liver and kidney. Notably, healthy and cancerous uterine cervical tissues express gene and protein levels of vitamin D receptor (VDR) and activating and catabolising vitamin D CYP450 enzymes, collectively comprising the autocrine vitamin D metabolism system (VDMS). Thus, in the uterine cervix, systemic vitamin D metabolism is complemented by the additive autocrine VDMS. The autocrine VDMS axis, therefore, may confer potential anticancer benefits by fine-tuning intracellular vitamin D metabolism involved in the downstream regulation of cell health genes. This chapter includes an overview of uterine cervical cancer and vitamin D metabolism, a brief description of the molecular mechanisms of vitamin D’s anticancer actions and an exploration of preclinical studies which have investigated the role of autocrine VDMS-mediated anti-tumorigenesis in uterine cervical cancer. Additionally, the potential chemotherapeutic implications of autocrine vitamin D metabolism in uterine cervical cancer are considered.