MilliporeSigma
  • 11-Methoxytabersonine Induces Necroptosis with Autophagy through AMPK/mTOR and JNK Pathways in Human Lung Cancer Cells.

11-Methoxytabersonine Induces Necroptosis with Autophagy through AMPK/mTOR and JNK Pathways in Human Lung Cancer Cells.

Chemical & pharmaceutical bulletin (2020-03-03)
Di Ge, Hong-Rui Tao, Lei Fang, Xiang-Qian Kong, Li-Na Han, Ning Li, Yan-Xin Xu, Ling-Yu Li, Mei Yu, Hua Zhang
ABSTRACT

Aspidosperma alkaloids, a subclass of monoterpenoid indole alkaloids rich in the Apocynaceae plants, possess remarkable antitumor activities, but the underlying mechanisms have rarely been reported. In the current project, 11-methoxytabersonine (11-MT), an aspidosperma-type alkaloid isolated from Tabernaemontana bovina, significantly inhibited the viability of two human lung cancer cell lines A549 and H157, and the molecular mechanisms were thus investigated. The results showed that 11-MT killed lung cancer cells via induction of necroptosis in an apoptosis-independent manner. In addition, 11-MT strongly induced autophagy in the two cell lines, which played a protective role against 11-MT-induced necroptosis. Finally, the autophagy caused by 11-MT was found to be via activation of the AMP activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) and the c-Jun N-terminal kinase (JNK) signaling pathways in both cells. Taken together, 11-MT exhibited an antitumor mechanism different from that of previously reported analogues and could have the potential to serve as a lead compound for the development of new chemotherapy for lung cancer.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acridine Orange hydrochloride solution, 10 mg/mL in H2O, >95.0% (HPLC)
Sigma-Aldrich
RPMI-1640 Medium, With L-glutamine, without sodium bicarbonate, powder, suitable for cell culture
Sigma-Aldrich
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
Sigma-Aldrich
Sulforhodamine B, acid form, laser grade, Dye content 95 %
Sigma-Aldrich
HOE 140, ≥94%
Sigma-Aldrich
Acridine Orange base, Dye content 75 %
Millipore
Immobilon®-PSQ PVDF Membrane, 10 sheets, 9 cm x 12 cm, 0.2 µm pore size, Hydrophobic PVDF Transfer Membrane for western blotting.