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

The discovery that the active form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)2D] 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)2D 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)2D3 (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)2D3 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)2D3 in the upregulation of p21 and p27, that in turn arrested HepG2 cells at the G0/G1 phase to a greater extent. Given that no active caspase 3 was detected and treatment with 1α,25(OH)2D3 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)2D3 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.

► MART-10, a vitamin D, analog, exhibits potent antiproliferation effect on HCC.
► MART-10 upregulates expressions of p21 and p27, slowing down the progress of cell cycle of HCC cells.
► The antiproliferation effect of MART-10 on HCC is apoptosis-independent.