Introduction: Lung, breast, and
colorectal cancers are the leading causes of
cancer-related deaths despite many therapeutic options, including targeted
therapy and
immunotherapies. Methods: Here, we investigated the impact of
PTC-209, a small-molecule Bmi-1 inhibitor, on human
cancer cell viability alone and in combination with anticancer drugs, namely,
cisplatin,
oxaliplatin,
5-fluorouracil,
camptothecin, and
Frondoside-A and its impact on cellular migration and colony growth in vitro and on
tumor growth in ovo. Results: We demonstrate that
PTC-209 causes a concentration- and time-dependent decrease in the cellular viability of
lung cancer cells (LNM35 and A549),
breast cancer cells (MDA-MB-231 and T47D), and
colon cancer cells (HT-29, HCT8/S11, and HCT-116). Similarly, treatment with
PTC-209 significantly decreased the growth of LNM35, A549, MDA-MB-231, and HT-29 clones and colonies in vitro and LNM35 and A549
tumor growth in the in ovo
tumor xenograft model.
PTC-209 at the non-toxic concentrations significantly reduced the migration of lung (LNM35 and A549) and breast (MDA-MB-231)
cancer cells. Moreover, we show that
PTC-209, at a concentration of 1 μM, enhances the anti-
cancer effects of
Frondoside-A in lung, breast, and
colon cancer cells, as well as the effect
camptothecin in
breast cancer cells and the effect of
cisplatin in
lung cancer cells in vitro. However,
PTC-209 failed to enhance the anti-
cancer effects of
oxaliplatin and
5-fluorouracil in
colon cancer cells. Treatment of lung, breast, and
colon cancer cells with
PTC-209 (1 and 2.5 μM) for 48 h showed no
caspase-3 activation, but a decrease in the cell number below the seeding level suggests that
PTC-209 reduces cellular viability probably through inhibition of cell proliferation and induction of cell death via a caspase-3-independent mechanism. Molecular mechanism analysis revealed that
PTC-209 significantly inhibited the STAT3 phosphorylation by decreasing the expression level of gp130 as early as 30 min post-treatment. Conclusion: Our findings identify
PTC-209 as a promising
anticancer agent for the treatment of solid
tumors either alone and/or in combination with the standard cytotoxic drugs
cisplatin and
camptothecin and the
natural product Frondoside-A.