Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including human prostate cancer and oral squamous cell carcinomas. ANO1 plays a critical role in tumor growth and maintenance of these cancers. In this study, we have isolated two new compounds (1 and 2) and four known compounds (3–6) from Mallotus apelta. These compounds were evaluated for their inhibitory effects on ANO1 channel activity and their cytotoxic effects on PC-3 prostate cancer cells. Interestingly, compounds 1 and 2 significantly reduced both ANO1 channel activity and cell viability. Electrophysiological study revealed that compound 2 (Ani-D2) is a potent and selective ANO1 inhibitor, with an IC50 value of 2.64 μM. Ani-D2 had minimal effect on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity and intracellular calcium signaling. Notably, Ani-D2 significantly reduced ANO1 protein expression levels and cell viability in an ANO1-dependent manner in PC-3 and oral squamous cell carcinoma CAL-27 cells. In addition, Ani-D2 strongly reduced cell migration and induced activation of caspase-3 and cleavage of PARP in PC-3 and CAL-27 cells. This study revealed that a novel ANO1 inhibitor, Ani-D2, has therapeutic potential for the treatment of several cancers that overexpress ANO1, such as prostate cancer and oral squamous cell carcinoma.

Promising activity against NTERA-2 cancer stem cells of malloapelta B compound isolated from the Bum-bup plant in Vietnam

Recent studies have revealed that cancer stem cells (CSCs) drive tumor growth, metastasis, therapy resistant and recurrence. Therefore, CSCs are considered as new targets for screening of more effective drugs. The compound malloapelta B, which was isolated from the Bum-bup plant (Mallotus apelta) (Lour.) Muel.-Arg, Euphorbiaceae) in Vietnam, presented very potent and strong anticancer invitro, especially against the activation ofNF-kB (nuclear factor- kappa B). In our research, malloapelta B inhibited the growth of NTERA-2 line, a CSC line, at the value of IC50 = 12.71 ± 0.76 µM. In this study, malloapelta B also had effects on cell cycle of NTERA-2 by significantly reducing the cell number at G0/G1 phase (37.48%), while raising this number of phase G2/M to 31.12% in comparison with those of control (56.81% and 18.6%, respectively). Besides, clonogenic and tumorspheroidal formations are acknowledged as typically renewable characteristics of CSCs. Then, in our studies, malloapelta B significantly prevented NTERA-2 to form clonogens and reduced tumorspheres’ sizes at treatments with 20 and 100 µg/mL. However, malloapelta B did not exhibit any obvious effects on the expression level of CD44+/CD24+, the two typical cell surface markers of CSCs, at 2.5 and 5 µM treatments.