title: 19-Nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10) is a potent cell growth regulator with enhanced chemotherapeutic potency in liver cancer cells.
abstract: The discovery that the active form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)(2)D] can modulate cellular proliferation and differentiation of cancer cells has led to its potential application as a chemotherapeutic agent to treat a variety of cancers. However, the use of 1α,25(OH)(2)D is limited due to its lethal side effect of hypercalcemia upon systemic administration. To overcome this drawback, numerous analogs have been synthesized. In this report, we examined the anti-proliferative activity of a new analog, 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)(2)D(3) (MART-10), in HepG2 liver cancer cells, and studied the potential mechanisms mediating this action. We found that MART-10 exhibited approximately 100-fold greater activity than 1α,25(OH)(2)D(3) in inhibiting HepG2 cell proliferation as determined by cell number counting method. MART-10 was also approximately 100-fold more potent than 1α,25(OH)(2)D(3) in the upregulation of p21 and p27, that in turn arrested HepG2 cells at the G(0)/G(1) phase to a greater extent. Given that no active caspase 3 was detected and treatment with 1α,25(OH)(2)D(3) or MART-10 did not further increase the fractions of apoptotic and necrosis cells over the controls, the growth-inhibitory effect of 1α,25(OH)(2)D(3) and MART-10 on HepG2 cells may not involve apoptosis. Overall, our findings suggest that MART-10 is a good candidate as a novel therapeutic regimen against liver cancer. Further pre-clinical studies using animal models and the subsequent human clinical trials are warranted.
authors: General Surgery Department of Chang Gung Memorial Hospital, Chang Gung University, Keelung, Taiwan.
authors: Kun-Chun
authors: KC
authors: Chiang
authors: Chun-Nan
authors: CN
authors: Yeh
authors: Huang-Yang
authors: HY
authors: Chen
authors: Jim-ming
authors: JM
authors: Lee
authors: Horng-Heng
authors: HH
authors: Juang
authors: Miin-Fu
authors: MF
authors: Chen
authors: Masashi
authors: M
authors: Takano
authors: Atsushi
authors: A
authors: Kittaka
authors: Tai C
authors: TC
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C569618:19-nor-2-(3-hydroxypropyl)-1,25-dihydroxyvitamin D3; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D014807:Vitamin D; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002762:Cholecalciferol; C097949:1,25-dihydroxyvitamin D